Abstracts Keynote & Plenary

Abstracts
Keynote & Plenary
KN-001
Whole-Genome Based Composition Vector Approach to Phylogeny
Bailin Hao
T-Life Research Center and Department of Physics, Fudan University, Shanghai 200433, China
Institute of Theoretical Physics, Academia Sinica, Beijing 100190, China
Santa Fe Institute, Santa Fe, NM 87501, USA
The composition vector approach (CVTree) is an alignment-free and almost parameter-free method to
infer phylogeny from whole-genome data. It has been successfully applied to phylogenies of viruses,
chloroplasts, prokaryotes, and fungi. In general, the phylogenetic trees obtained by CVTree method
agree with the latest taxonomies in an overwhelming cases of major and fine branchings, while the
disagreements often reveal problems debated by biologists for years and hint on possible taxonomic
revisions. However, as a new and non-traditional approach, many questions remain to be answered
regarding the foundation of this method. In this talk we will touch on a few of these questions, for
example, the relation between the collection of K-peptides and the primary protein sequences, the
calibration of branch lengths in CVTrees, the choice of an optimal peptide size for constructing the
composition vectors, and the statistical tests of the trees (bootstrapping, jackknifing, and
anti-jackknifing).
KN-002
Stochastic Simulation of Biomolecualr Networks based on Hybrid Systems
Luonan Chen 1,2,3
, Ruiqi Wang 3
, Kazuyuki Aihara 2
1Department of Electrical Engineering and Electronics, Osaka Sangyo University, Osaka, Japan.
2 Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
3Institute of Systems Biology, Shanghai University, Shanghai, China.
Explicitly considering all variables and chemical reactions in a cell is unrealistic for a gene regulatory
network from modeling, analyzing and computing viewpoint. However, in a cell, many different time
scales characterize the gene regulatory processes, which can be exploited to reduce the complexity of
the mathematical models. For instance, the transcription and translation processes generally evolve on a
time scale that is much slower than that of phosphorylation, dimerization or binding reactions of
transcription factors. Moreover, in biological systems, a large class of biological models can be
approximately by stochastic hybrid systems in which some state components are discrete and other are
continuous. Continuous state components are usually involved in fast reactions with high copy
numbers of molecules, whereas discrete state components are in slow processes and have low copy
numbers of molecules. In this work, based on the partial Kramers-Moyal expansion with the central
limit theorem, we exploit such properties to simplify a complicated molecular network to a hybrid
system by giving several models, which can be applied to the quantitative simulation of a large cellular
system. In other words, we developed a novel stochastic hybrid model for representing chemical master
equation, and provide several computational algorithms to efficiently simulate the stochastically
cellular dynamics.
Conical intersections and new atomic-level reaction mechanisms

Wensheng Bian, Jianwei Cao, Haitao Ma, Xiaojun Liu, Chunfang Zhang
Institute of Chemistry, Chinese Academy of Sciences.
Zhongguancun North First Street 2,100190 Beijing, P. R.
China.
Conical intersections (CIs) play a key role in electronically nonadiabatic
processes [1]. From gas
phase
to condensed phase, from small systems with three or four atoms to biomolecules such as DNA
and protein, the ultrafast nonadiabatic processes induced by CIs are ubiquitous. For example, in the
study of green fluorescent protein, as long as very short excited-state lifetime is observed, it is always
attributed to an ultrafast internal conversion resulting from CI. The C(1D)H2 system exhibits
interesting nonadiabatic dynamical features, including Renner-Teller effects and multiple conical
intersections. It thus serves as an important prototype for ultrafast nonadiabatic processes. CIs and
geometric phase effects among the 11A', 21A', 31A', 11A'', and 21A'' states are carefully investigated
and valuable insights are obtained.
Molecular dynamics simulations have become a powerful tool for the study of biological
macromolecules. On the other hand, classical mechanics- based methods have been shown to be
very useful in elucidating detailed atomic-level mechanisms. Here, quasiclassical trajectory (QCT)
calculations are performed to reveal new atomic-level mechanisms of polyatomic abstraction and
exchange reactions. The accurate global ab initio potential energy surface constructed by us [3] is
used, which describes both the H+SiH4 abstraction and exchange reactions. Our QCT studies
reveal interesting features of detailed dynamical quantities and underlying new reaction
mechanisms. We designate the new mechanisms for exchange found by us as torsion-tilt and
side-inversion. The abstraction reaction is shown to be a combination of rebound and stripping.
These findings are important for acquiring a deeper understanding of reaction dynamics.
[1] X.
Liu, W. Bian, X. Zhao, X. Tao, J. Chem. Phys. 2006, 125, 074306.
[2] M. Wang, X. Sun, W. Bian, J. Chem. Phys. 2008, 129, 084309.
[3] J. Cao, Z. Zhang, C. Zhang, K. Liu, M. Wang, W. Bian,
Proc. Natl. Acad .Sci. U.S.A. 2009, in press (doi:10.1073/pnas.0903934106).
PL-002
Towards Predictive
Stochastic Dynamical Modeling of Cancer Genesis and Progression
P. Ao
Laboratory of Systems Biomedicine of Ministry of
Washington, Seattle, WA 98195,
te for Systems Biology, 1441 N. 34 St., Seattle, WA 98103, USA.
1,2,
D. Galas 3
, L. Hood 3
, L. Yin 4
, X.-M. Zhu 5
1 Shanghai Center for Systems Biomedicine, Key
Education, Shanghai Jiao Tong University, Shanghai 200240, China
2 Departments of Mechanical Engineering and Physics, University of
USA
3 Institu
4 School of Physics, Peking University, Beijing 100871, China
5 GenMath, Corp. 5525 27th Ave.N.E., Seattle, WA 98105, USA.
Here we wish to advance an evolutionary and stochastic dynamics formulation of carcinogenesis.
The novel biological hypothesis behind such formulation has been stated in our previous
publication [1]: Cancer as an intrinsic robust state of the endogenous network not optimized for
the interest of whole organism. More explicitly, the molecular and cellular agents, such as
oncogenes and suppressor genes, and related growth factors, hormones, cytokines, etc, form a
nonlinear, stochastic, and collective dynamical network, the endogenous molecular‐‐cellular
network. This endogenous network may be specified by the expression or activity levels of a
minimum set of endogenous agents, resulting in a highdimensional stochastic dynamical system.

The nonlinear dynamical interactions among the endogenous agents can generate many locally stable
states with obvious or non-obvious biological functions. The endogenous network may stay in any of
such stable state for a considerably long time. In this manner the endogenous network is able to
autonomously decide its operational functioning state. Some states may be normal, such as cell growth,
apoptosis, arresting, etc. Others may be abnormal, such as growth with elevated immune response and
high energy consumption, likely the signature of cancer, or of still useful functions to deal with
occasional stressful situations. The stochasticity may accidentally cause a transition from one stable
state to another. If with a given condition the endogenous network is in a state not optimized for the
interest of whole organism, the organism is ‘sick’, though this state might be ‘normal’ under other
conditions. Through the identifying agents of this endogenous network, the delineating of its wiring
rules among endogenous agents, and the elucidating its global dynamical properties, a systems
understanding of both normal and abnormal behaviors on how a tissue functions may be reached.
PL-003
Density-functional calculations for large systems: can GGA functionals be competitive with
hybrid functionals?
damo 1
and Pietro Cortona 2
Vincent Tognetti
UMR 7575, Ecole Nationale Supérieure de
0, Ecole Centrale Paris,
and RevTCA, belonging to the
1
, Carlo A
1.Laboratoire d’Electrochimie et de Chimie Analytique,
Chimie de Paris, 11 rue P. et M. Curie, F-75231 Paris Cedex 05, France.
2.Laboratoire Structure, Propriété et Modélisation des Solides, UMR 858
Grande Voie des Vignes, F-92295 Châtenay-Malabry, France.
Two recently proposed correlation functionals, TCA
generalized-gradient approximation (GGA) class, are briefly presented and their performances are
discussed. The emphasis is put on the comparison with hybrid functionals, which are often the
preferred ones for applications to molecular (but not to solid-state) systems. We show that the TCA and
RevTCA performances are not far from those of hybrid functionals such as B3LYP or PBE0 when
standard tests are performed and can be even better when less standard systems are considered. This is
particularly interesting in view of applications to nano-scale systems or systems of biological interest,
and, in general, in all the cases where the computer time requirements become an important constraint.
lar modeling and structural and biocatalytic properties of biogene amines
kov 1,2
Keywords: Density-functional theory; correlation functionals; GGA functionals; hybrid functionals;
atomization energies; activation energies for chemical reaction; hydrogen bond
PL-004
Biomolecu
(patophysiology)
Alexander V. Glush
1Odessa University, P.O.Box
24a, Odessa-9, SE, 65009, Ukraine
2Russian Academy Sciences, Troitsk, Moscow reg., 142090, Russia
E-mail: glushkov@paco.net Paper is devoted to the Monte-Carlo
computational studying the structural, and spectro
properties for the biomolecules, in particular, biogene amines: serotonine (ST), histamine (HM), γ-amino oil acid (AC) a
laser and neutron capture action on the indicated properties of studied molecules. The ST (or 5-hydroxitriptamine, 5-H
produced by means of the hydroxciliration of essencial amine acid of the triptophane [1]. ST influences mainly in a place
of
its appearance and calls for blood vessel narrowing in places of the trombocites decay. Probably,
serotonine ST is the mediator for transition of the nervous pulses in some branch of the brain. HM

is produced in cells (mastocides) from the histidine amino acid. The γ-amino oil acid AC is
produced in the brain substance and probably plays a role of the mediator or inhibitor of pulses.
Many biomolecules (BM) are composed not only by hydrophilic, but also by hydrophobic groups,
in the vicinity of which the water-water (or blood plasma) interaction is expected to be present
even in the zeroth approximation. We present results of the Monte-Carlo calculating the cluster
consisting of the serotonine ST (histamine HM) molecules and 100 molecules of water. All
relevant interaction potentials are obtained by means of quantum calculation [1]. The water-water
interaction potential was found by Matsouka etal by CI method. The BM-water interaction
potential was obtained in the SCF approximation Calculation is carried out at T=300K; All
molecules are treated as rigid. The results for interaction energies are given below in table:
Potential, kJmol-1
Neutral molecule
zwitterion
Water-water
-27.7 ± 0.8
-27.2 ± 0.7
ST-water
-59.5 ±2.0
-348.5 ± 15.0
HM-water
-37,8 ±2.0
-178,4 ± 15.0
The zwitterion appears as expected to be strongly favoured with respect to neutral molecule. The
HM in the “zwitterion” more intensively (on the order) catalyses the gastric juice secretion and
secretion from other endocrine glands. The similar situation is with action of the HM in the
inflammatory and allergic reactions with further increasing vessel walls permeability and action of
the ST with further blood-vessel narrowing in places of the trombocites decay [2]. We at first
consider the possibilities of laser and neutron capture action on different of molecules, including
an analysis of Szilard-Chalmers (n,γ), (n,n), Mössbauer and GM [2] effects. Some new
bio-nano-technologies are analysed.
References:
[1] E. Clementi
et al, Gazz. Chim. Ital. 108 (1978) 157-174; J. Am.Chem. Soc. 99 (1977) 5531-42 ;
A.Glushkov, Journ.Struct. Chem. 34 (1993) 3-10; 31 (1990) 9-15; 32 (1992) 11-16; Rus. J. Phys.
Chem. 66 (1992) 1259-76; 66 (1992) 589-596; A. Glushkov, S.Malinovskaya, Rus. J. Phys. Chem.
62 (1988) 100-106; 65 (1991) 2970-78;
[2] A. Glushkov, S.Malinovskaya, In: New
projects and new lines of research in nuclear physics.
Eds. G.Fazio and F.Hanappe, Singapore : World Scientific.-2003.-P.242-250 ; Int.J.Quant.Chem 99
(2004) 889-896 ; 104 (2005) 496-500; Europ.Phys.Journ. 160 (2008) 195-208 ; Mol.Phys. (UK),
106 (2008) 1257-1262 ; A. Glushkov, Comput. Life Sciences (Springer), to be submitted (2009);
PL-005
Understanding
disease-associated amino acid mutations with computational models
Shen, Bairong
PL-006
Physico–
chemical principles governing biological processes

Lim., Carmay
Our research interests are to unravel the underlying physico–chemical principles governing
biological processes, develop new methods, as required, along the way and use the above
principles and methods to design molecules with potential therapeutic utility. This talk will
provide an example of work in these three areas by unraveling the physical basis underlying
structural and catalytic Zn−binding sites in proteins.
References:
1.“Physical Basis
of Structural and Catalytic Zn−binding Sites in Proteins”. Yu-Ming Lee & Carmay
Lim*, J. Mol. Biol. (2008) 379:545–553.
2.“Metal Binding Affinity and Selectivity in Metalloproteins: Insights from Computational Studies”.
Todor Dudev & Carmay Lim*, Annual Reviews in Biophysics. (2008) 37:97–116
3.“Effect of Carboxylate–Binding Mode on Metal Binding/Selectivity and Function in Proteins”.
Todor
Dudev & Carmay Lim*, Acc. Chem. Res. (2007) 40: 85−93.
4.“Principles Governing Mg, Ca, and Zn Binding and Selectivity
in Proteins”. Todor Dudev* &
Carmay Lim*, Chemical Reviews (2003) 103: 773–787.
PL-007
A novel Locally Linear Embedding and Wavelet Transform based encoding method for
prediction of MHC-II binding affinity
Juan Liu 1*
, Qingjiao Li 1
, Wen Zhang 1
1 School of Computer Science, Wuhan University,
Wuhan 430079, China
* Corresponding author
The binding between peptides
and MHC molecules is an important event to the cellular immunity
against pathogens. The binding peptides are recognized as the epitopes, which are useful for the
epitope-based vaccine design. Accurate prediction of the MHC-II binding peptides has long been a
challenge in bioinformatics. Recently, most researchers are interested in predicting the binding affinity
instead of categorizing peptides as “binders” or “non-binders”. In this paper, we introduced a novel
encoding scheme based on Locally Linear Embedding (LLE) and Wavelet Transform (WT), in which
important amino acid properties were firstly selected from all properties (described in AAindex
database) by using LLE, and then amino acids of peptides were replaced with these novel properties.
Further, WT was adopted to extract the frequency attributes of the numerical sequences; thereby the
peptides were transformed into homogeneous-length vectors. Finally, Support Vector machine
Regression (SVR) was used to make quantitative prediction models based on these numerical vectors.
When applied to the 17 datasets from IEDB database, our encoding scheme produced consistently
better performance than other encoding schemes, indicating that our encoding scheme is an effective
tool for the prediction of MHC-II binding affinity.
Keywords: Cellular immunity; Epitopes; MHC-II binding
affinity; Support Vector machine Regression; Locally
Linear Embedding; Wavelet Transform; Encoding method
PL-008
Nakai, Kenta
PL-009
Nanopolaritonics: the interaction between molecules and near-field light.
Daniel Neuhauser,

Chemistry and Biochemistry Department, UCLA, Los Angeles, CA 90095-1569
As nanoscale experiments continually shrink in size, the scale over which light moves becomes closer
and closer to molecular scale. At present, metal particles with a diameter of a few nanometers can be
fabricated and placed in arrays. We show that at these scales, molecules can have significant dipole
moment to stir the near-field light propagated between the molecules. This is an example of what we
label as nanopolaritonics, the combined action of metal plasmons and molecular excitations. The
versatility and controllability inherent in molecules, when combined with the large dipole moments
of
metal plasmons, can therefore be combined to stir and modulate light on the nano and sub-nano scale.
PL-010
In silico Modeling
of Wnt Signaling Pathway: Effects of GSK3� Phosphorylation, -catenin
Phosphorylation, and -catenin Degradation in Kinetics
Ying-Chieh Sun
Department of Chemistry,
National Taiwan Normal University, 88, TingChow Road Section 4, Taipei
116, Taiwan
Email address: sun@ntnu.edu.tw
Background
Recent experiments have explored effects of activities of kinases other than the well-studied kinase,
GSK3, in the signaling of wnt pathway, particularly in the level of -catenin. In addition, it was
found that the kinase PKA can attenuate degradation of -catenin. However, the role of these
kinases in the level of -catenin, degradation of -catenin, and the resulting downstream transcription
activity remains to be clarified. Furthermore, the effect of GSK3 phosphorylation in -catenin
level was not examined computationally. In the present study, effects of phosphorylation of GSK3,
�phosphorylations and degradation of -catenin in the kinetics of wnt signaling pathway were
examined computationally.
Methods
The well-known
computational Lee-Heinrich kinetic model of wnt pathway was modified to include
these effects. The rate laws of reactions in the modified model were solved numerically to examine
these effects in -catenin level.
Results
The computations
gave that the -catenin level is almost linearly proportional to the
phosphorylation activity of GSK3. The dependence of -catenin level on activity of
phosphorylation and degradation of free -catenin and downstream TCF activity can be analyzed
with an approximate, simple function of kinetic parameters of added reaction steps associated with
examined effects in order to rationalize observed experimental results.
Conclusions
The phosphorylations
of -catenin by kinases other than GSK3 should take place at free
unphorphorylated -catenin instead of the GSK3 -phosphorylated -catenin*. In order
to
account for observed enhanced TCF activity, the step of -catenin dephosphorylation is essential, and
the kinetic parameters of -catenin phosphorylation and degradation need to meet a condition,
describing in the text below. These findings should be useful for future experiments.
PL-011
Computational
Drug Design for Cancer Using Tubulin as a Target
Jack A. Tuszynski
Cross Cancer Institute,
Edmonton, Alberta, Canada

Email: jtus@phys.ualberta.caBackground/Problem:
The ultimate goal of cancer research is to
develop a drug or treatment regimen that will target only cancer cells with minimal damage done to
healthy tissues. The significance of microtubules as a molecular target for chemotherapeutic treatments
is outlined in a recent review [1]. Tubulin which makes up microtubules binds numerous small
molecule ligands, which result in the alteration of microtubule dynamics leading to cell cycle arrest and
cell death. Many of these ligands are currently used clinically for the treatment of several types of
cancer and include the drugs paclitaxel, colchicine and vinblastine. These drugs bind to one of three
distinct binding sites within beta tubulin, all of which have been recently identified through electron
crystallography. The drawback of these drugs is their indiscriminate binding to all cells leading to the
death of both cancerous and healthy cells. Hence despite the overall success of the vinca alkaloid and
taxane drug families side effects such as neurodegradation seriously impair the prognosis for many
cancer patients treated with them. Moreover, in many cases drug resistance develops in the course of
chemotherapy.
Tools and Methods:
We have focused on computational searches, optimization and testing new and
re-purposing old molecules that interfere with the formation of mitotic spindles during cell division in
tumors. To build the molecular models of our target tubulin, we used the program Modeller [2] that
uses alignment of the sequences with known related structures to obtain spatial restraints that the output
structure must satisfy. Missing regions are predicted by simulated annealing of a molecular mechanics
model. Only the default parameters of Modeller were used, as simple manual inspection of some of the
output structures suggests that reasonable models were produced.
Results: The existence and distribution of various tubulin isoforms is the basis for novel
chemotherapeutic drug design that can differentiate between different cell types to reduce side effects.
The quality of the resulting models for tubulin isoforms was investigated using two software packages
WHAT_CHECK [3] and PROCHECK [4] followed by an analysis of ten human beta tubulin isoforms
regarding their differences within each of the determined paclitaxel, colchicine and vinblastine binding
sites. New promising compounds representing taxane and colchicine derivatives have been designed
and computationally tested for isoform specificity and will be presented at this conference. They have
been synthesized and are being tested in our lab. The stabilities of these derivatives have been
computationally evaluated using both classical and quantum mechanical methods. In addition, based on
the mechanical properties of microtubules we are working on new treatment modalities that use
ultrasound, laser action and magnetic fields directly on cells.
Conclusions/Discussion: Significant progress has been made in our understanding of the key cellular
target for chemotherapy: tubulin. Based on our computational models, we have designed several dozen
new promising compounds that selectively bind to tubulin isoforms that reflect patient-specific
mutations in tumor cells. Our future plans include a massive computational effort to match every target
protein with an existing chemical entity.
References
[1] M.A. Jordan and L. Wilson (2004) Nature Rev. Cancer 4, 253-265.
[2] R. Sanchez and A. Sali, 2000, Methods Mol Biol, 143, 97-129
[3] R.W.W. Hooft et al., 1996, Nature, 381, 272
[4] R.A. Laskowski et al., 1993, J. Appl. Cryst, 26,
283-291
Acknowledgements: This project has been funded by MITACS,
the Allard Foundation, NSERC,
PIMS, CPCRI, US Department of Defense, Oncovista LLC (San Antonio, TX) and Technology
Innovations LLC (Rochester, NY).

Quantum-based Accurate Electrostatic Interaction for Proteins with Polarization
John Z.H. Zhang
State Key Laboratory
of Precision Spectroscopy, Department of Physics, East China Normal
University
Department of
Chemistry, New York University, New York, NY 1000, USA
Email: john.zhang@nyu.edu
Efficient fragment-based quantum
mechanical method for accurate calculation of protein in solution is
developed and applied to study protein structure and dynamics. The quantum calculation of protein is
further employed to generate new force field that features polarized protein-specific charges (PPC).
The PPC provides a realistic description of the polarized electrostatic state of the protein than the
widely used mean field charges such as AMBER and CHARMM. Extensive MD simulations have been
performed to study the efficacy of PPC through direct comparisons between results obtained from PPC,
the standard AMBER charges and experimental results. The impact of PPC on protein electrostatic
interaction, stability of hydrogen bonds, protein-ligand binding and protein dynamics are presented in
this talk. The results clearly demonstrate that the correct description of the electronic polarization of
protein is crucial and PPC shall have important applications for MD simulation studies of protein
structure and dynamics.
PL-014
Development
of formula nutrient/drug technology to transform local molecular network patterns
Zhizhou Zhang
titute for Technology, Weihai 264209
would display the associations among the following concepts:
genes closely associated with it. Those genes are naturally linked
ttern (LGNP)
extremely important to classify local molecular network
er of LGNP or LMNP. The disease state and normal state would
ct or indirect molecular linkages with one or several nutrient metabolic
1,2
,Pengpeng Li 2
, Liangyu Meng 2
, Lin Huang 2
1BIO-X Center for Ocean Systems Biotechnology, Harbin Ins
2Teda Bio-X Center for Systems Biotechnology, Tianjin University of Science and Technology,
Tianjin 300457
This presentation
Local molecular network (LMN)
Any biological phenotype has a set of
with each other with several ways (routes): signal transduction pathway, protein-protein interaction,
protein-nucleic acid interaction, or metabolic reactions. So finally any phenotype has a specific local
molecular network in which genes, proteins and metabolites interact with each other into a dynamic or
static LMN structure.
Local gene network pa
High-throughput experimental data are
patterns. cDNA microarray data can help to decipher local gene network patterns.
Network pattern transformation
A complex disease has a large numb
both have several or a set of LMNP. How to transform the diseased LMNP to the normal LMNP with
drug or food is of interest.
Nutrient module linkage
Any LMNP would have dire
modules, such as amino acid metabolism, nucleic acid metabolism, vitamin and cofactor metabolism,
fatty acid metabolism, etc. If a LMNP is closely inked with three different nutrient metabolic modules,
it is expected that the combination of the three different nutrients has a potential to modulate the LMNP
states.

Formula drug or nutrient
Any LMN is surrounded by several nutrient metabolic modules or molecular interaction routes. The
combination of someregulators or food nutrients to modulate the activities of such modules or routes,
thus leading to transformation of target LMNPs, will automatically lead to formula drug or formula
nutrient.
Quantitative
approaches
Development of formula
drug or formula nutrient is highly dependent on characterization and
manipulation of nonlinear behavior of cellular molecular network. Such quantitative approaches are
essential for individual formula nutrient/drug development platform. But at present, high-throughput
data may be more needed.
References
[1] Ping Ao,
Lik Wee Lee, et al. Towards Kinetic Modeling of Global Metabolic Networks:
Methylobacterium extorquens AM1 Growth as Validation. Chin J Biotech, 2008, 24(6), 980−994.
[2] E. Almaas et al. Global organization of metabolic fluxes in the bacterium E coli. Nature 467(2004),
839-843.
[3] Zhizhou
Zhang, Yun Wang, et al. Local gene network pattern (LGNP) approach to tackle
mechanisms of complicated phenotypes: local network structure of hypertension related genes. The 2nd
International Conference on Bioinformatics and Biomedical Engineering, 2008.
[4] Liangyu Meng, Pengpeng Li, Zhizhou Zhang. Gene network study revealed molecular links among
genes for alcohol metabolism and breast cancer susceptibility. The 3rd International Conference on
Bioinformatics and Biomedical Engineering, 2009.
[5] This study was supported by 2006 NECT grant and
Ocean BIO-X start-up fund to ZZZ.
PL-015
Integrated Approaches to Mapping Genome to Phenome
Xianghong Zhou,
University of Southern
California
The rapid accumulation of genomics data provides unprecedented opportunities to systematically infer
genetic networks and phenotype associations. In this talk, I will report our recent efforts in utilizing the
enormous amount of public genomics data, together with the associated phenotypic and environmental
context information, to reconstruct the biological basis of phenotypes. Traditional association studies
have been relatively successful at relating genetic polymorphisms to phenotypes. However, they have
met difficulties in elucidating the gene-gene interactions that contribute to complex phenotypes. Here,
we develop novel methods aimed at deriving genome-wide molecular networks of genotype-phenotype
associations. Furthermore, we develop methods to perform phenotype prediction and computational
diagnosis utilizing public genomics databases, particularly the large public microarray repositories, to
create an automated disease diagnosis database.
PL-016
Methylomic
aspects of life in health and diseases
Jingde Zhu,
The Cancer Epigenetics
and Gene Therapy Program, The State-key Laboratory for Oncogenes and
Related Genes, Shanghai Cancer Institute, Shanghai 200032, China
Email: zhujingde@gmail.com, zhujingde@shsci.org,
DNA methylation is an important and reversible epigenetic modification, which regulates the
genome transcription and therefore cell fate and phenotype. Faithful DNA methylation is

essential for mammalian development and health, Perturbation of its dynamics contributes to all
the major disease, including cancer. The discovery by the latestcutting-edging methylomic
approaches and following validation of the epigenetic biomarkers (DNA methylation) in the quality
clinic setting are essential to better stratify the disease and rationale use of therapeutics. In this
presentation, the vital importance of the epigenetic researches to the today’s life science will be
discussed with our own works as paradigms: 1, The potential of DNA methylation biomarker in bodily
fluids for cancer detection and prediction (bladder cancer and lung cancer); 2, the MBD affinity
approaches/the 2nd generation technologies for both low and the sequence resolution methylome in
both health and disease of human; and 3, the first high resolution methylome of the human peripheral
blood mononuclear cells by bisulphite sequencing.
PL-017
Signatures of low-dimensional chaos in the human heartbeat dynamics
Alexander V. Glushkov
ox 24a, Odessa-9, SE, 65009, Ukraine
1,2
1Odessa University, P.O.B
2Russian Academy Sciences, Troitsk, Moscow reg., 142090, Russia
E-mail: glushkov@paco.net
This paper investigates the existence of chaotic behaviour in the human heartbeat dynamics. The
mutual information approach, the correlation integral analysis, the false nearest neighbour algorithm,
the Lyapunov exponents analysis, and the surrogate data method were used in the analysis (the details
of our versions are presented in refs.[1]). In ref. [2] we will firstly adapt the cited methods in the
computational biology and physiology.
The mutual information approach provided
a time lag which is needed to reconstruct phase space. Such
an approach allowed concluding the possible nonlinear nature of process resulting in the heartbeat
amplitudes variations. The correlation dimension method provided a low fractal-dimensional attractor
thus suggesting a possibility of the existence of chaotic behaviour. Based on the attractor dimensions,
the minimum number of variables essential to model the heartbeat amplitudes dynamics for two kinds
of people (absolutely healthy and hypertonic carrier). Significant improvement can be achieved when
additional variables, up to the number of variables sufficient (6), are included in the model. The method
of surrogate data, for detecting nonlinearity, provided significant differences in the correlation
exponents between the original data series and the surrogate data sets. This finding indicates that the
null hypothesis (linear stochastic process) can be rejected. The results from the aforementioned
methods indicate that the heartbeat amplitudes variations exhibits (and hypertonic carrier) a nonlinear
behaviour and possibly low-dimensional chaos. Thus, a short-term prediction based on nonlinear
dynamics is possible. The Lyapunov exponents analysis supported this conclusion. It can be noted that
the nonleading exponents are notoriously difficult to estimate from time series data. Moreover, the
interpretation of inverse Lyapunov exponents as predictability times can results in ambiguous
conclusions. In fact, the degree of instability and predictability can vary considerably throughout phase
space. Though a large number of studies employed the ideas gained from the science of chaos, there
have also been widespread criticisms on the application of chaos theory. Important reasons for this are:
(1) the assumptions with which the chaos identification methods have been developed, i.e. infinite and
noise-free time series; and (2) the inability of the investigative methods to provide irrefutable proof
regarding the existence of chaos. On the one hand, the basis for the criticisms of studies investigating
and reporting existence of chaos in the heartbeat dynamics is our strong belief that they are influenced
by a large number of variables and, therefore, are stochastic. On the other hand, the outcomes of the

present study provide support to the claims that the (seemingly) highly irregular processes could be the
result of simple deterministic systems with a few degrees of freedom. Therefore, the hypothesis of
chaos in our system is reasonable and can provide an alternative approach for characterizing and
modelling the dynamics of processes resulting in the heartbeat amplitudes variations.
References:
[1] A.V.Glushkov et al, Environm. Inf.Arch. 1 (2003) 125-130; Journ. of Hydr. 322 (2006) 14-24;
Quart.J.Royal Met.Soc.132 (2006) 447–465; Adv.Space Research. 42 (2008) 1614-1617 ; Atm.
Environm. (Elsevier) 42 (2008) 7284–7292; Stoch. Env. Res. Risk. Assess (Springer) 22 (2008)
777-788
[2] A. Glushkov,
Comput. Life Sciences (Springer), to be submitted (2009);
PL-018
Quantum Mechanical Effect in Protein-Ligand Interaction
Ke-Li Han
State Key Laboratory
of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese
Academy of Sciences, Dalian 116023, People's Republic of China
In this work, we have presented three examples to illustrate applications
of quantum mechanical
(QM)-based methods to studying QM effect in protein-ligand interaction. First, the QM calculation
based on the density functional theory (DFT) has been used to study the simplified active site model of
cytochrome P450 (CYP450) with ethanol molecule. Second, one of combined quantum mechanical and
molecular mechanical (QM/MM) methods, generalized hybrid orbital (GHO) approach was applied to
explore the identity of the fourth ligand of zinc in active site. Third, by molecular fractionation with
conjugate caps (MFCC) approach with full QM calculations, we obtain the interaction energies of
thrombin-inhibitor complexes. These studies show that QM-based method can play a major role in
elucidating the protein-ligand interactions. It is anticipated that QM-based method will be of significant
help in application to structure-based drug design.
PL-019
Kurnikova,
Maria
PL-020
Song, Youtao
PL-021
Computational
Investigation of the Anti-HIV Activity of Chinese Medicinal Formula
Three-Huang Powder
Li Bai1, Dagang Chen 2, Lanxiang Dong 2, Xuhong Wang 2, Qitai Xu3, W. M. Southerland, Zengjian
Hu
1.Department
of Drug Discovery and Development, Taney Academy of Sciences, Gaithersburg, MD
20877, USA
2.Amina International
Inc., Brooklyn, NY 11214, USA
3.Institute of Natural Products, Henan University, Kaifeng 475004, China
Department of Biochemistry and Molecular Biology, Howard University
College of Medicine,
Washington, DC 20059, USA
Email:zhu@howard.edu
An essential step in the life cycle of human immunodeficiency virus type 1 (HIV‐1) is integration
of the double‐stranded retroviral DNA into the genome of the host cell. HIV‐1 integrase, the

enzyme that inserts the vital DNA into the host chromosome, is an attractive and rational target
for anti‐AIDS drug design because it is essential for HIV replication and there are no known
counterparts in the host cell. Inhibitors of this enzyme have the great potential to complement
the therapeutic use of HIV protease and reverse transcriptase inhibitors. Natural products have
provided a source of new drugcandidates for anti-AIDS therapy. The number of compounds
exhibiting anti-HIV activity and isolated from natural sources has increase steadily. Baicalein and
baicalin, identified components of a Chinese herbal medicine Scutellaria baicalensis Georgi, have been
shown to inhibit infectivity and replication of HIV. They are therefore promising lead compounds for
developing new anti-AIDS drugs. To understand how the inhibitors work and therefore design more
potent and specific inhibitors, we have used molecular modeling techniques to investigate the binding
modes of these inhibitors. The three-dimensional structures of these inhibitors were first built. Then,
computational binding studies of these inhibitors, based on the crystal structure of the HIV-1 integrase
catalytic domain, were performed to study the complex structure. The preliminary results of our
computational modeling study demonstrated that Baicalein binds to the active site region of the HIV-1
integrase. Our study will be of help to identify the pharmacophores of inhibitors binding to HIV-1
integrase and design new pharmaceuticals for the treatment of AIDS.
Keywords: HIV-1 integrase, anti-AIDS drug, molecular modeling, baicalein.
Oral Presentation
OR-001
Prediction of non-classical secreted proteins using informative physicochemical properties
Chiung-Hui Hung
nchu,
s Biology, and Department of Biological Science and
1
, Hui-Ling Huang 2
, Kai-Ti Hsu 3
, Shinn-Jang Ho 4
and Shinn-Ying Ho 5
*
1.The Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsi
Taiwan (thesedays.h@gmail.com).
2. The Institute of Bioinformatics and System
Technology, National Chiao Tung University, Hsinchu, Taiwan (hlhuang@mail.nctu.edu.tw).
3. The Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu,
Taiwan (cafehe.bi96g@g2.nctu.edu.tw).
4. The Department of Automation Engineering,
National Formosa University, Yunlin 632, Taiwan
(sjho@nfu.edu.tw).
5. The Institute of Bioinformatics
and Systems Biology, and Department of Biological Science and
Technology, National Chiao Tung University, Hsinchu, Taiwan (syho@mail.nctu.edu.tw).
The prediction of non-classical secreted proteins is a significant problem for drug discovery and
development of disease diagnosis. The characteristic of non-classical secreted proteins is they are
leaderless proteins without signal peptides in N-terminal. This characteristic makes the prediction of
non-classical proteins more difficult and complicated than the classical secreted proteins. We identify a
set of informative physicochemical properties of amino acid indices cooperated with support vector
machine (SVM) to find discrimination between secreted and non-secreted proteins and to predict
non-classical secreted proteins. When the sequence identity of dataset was reduced to 25%, the
prediction accuracy on training dataset is 85% which is much better than the traditional sequence
similarity-based BLAST or PSI-BLAST tool. The accuracy of independent test is 82%. The most
effective features of prediction revealed the fundamental differences of physicochemical properties
between secreted and non-secreted proteins. The interpretable and valuable information could be
beneficial for drug discovery or the development of new blood biochemical examinations.

Keywords: Amino acid index, non-classical secreted protein, SVM prediction
Enhancing MEDLINE document clustering by incorporating MeSH semantic similarity
Shanfeng Zhu
School of Computer
Science, Fudan University, Shanghai 200433, China
Motivation: Clustering MEDLINE documents is usually conducted by the vector space model, which
computes the content similarity between two documents by basically using the inner-product of their
word vectors. Recently, the semantic information of MeSH (Medical Subject Headings) thesaurus is
being applied to clustering MEDLINE documents by mapping documents into MeSH concept vectors
to be clustered. However, current approaches of using MeSH thesaurus have two serious limitations:
first, important semantic information may be lost when generating MeSH concept vectors, and second,
the content information of the original text has been discarded.
Methods: Our new strategy includes three key points. First, we develop
a sound method for measuring
the semantic similarity between two documents over the MeSH thesaurus. Second, we combine both
the semantic and content similarities to generate the integrated similarity matrix between documents.
Third, we apply a spectral approach to clustering documents over the integrated similarity matrix.
Results: Using various 100 datasets of MEDLINE records, we conduct extensive experiments with
changing alternative measures and parameters. Experimental results show that integrating the semantic
and content similarities outperforms the case of using only one of the two similarities, being
statistically significant. We further find the best parameter setting that is consistent over all
experimental conditions conducted. We finally show a typical example of resultant clusters, confirming
the effectiveness of our strategy in improving MEDLINE document clustering.
OR-003
A new mechanical
algorithm for calculating the amplitude equation of the reaction-diffusion
systems
Houye Liu,
Weiming Wang
In this paper, we establish a new
mechanical algorithm AE Hopf for calculating the amplitude equation
near Hopf bifurcation based on the method of normal form approach. The results indicate that the
algorithm is simple and effective. This will be useful for learning the dynamics of pattern formation of
reaction-diffusion systems further.
Keywords: Amplitude equation, Mechanical
algorithm, Reaction-diffusion system
OR-004
Chaos game
representation of mitochondrial genomes: Markov Chain model simulation and
vertebrate phylogeny
Guo-Sheng Han1, Zu-Guo
Yu1,2,*, Bo Li1, Vo Anh2 and Yi-Quan Li1
1School of Mathematics and Computational Science, Xiangtan University,
Hunan 411105, China.
2School of Mathematical Sciences, Queensland University of Technology, GPO Box 2434, Brisbane,
QLD 4001, Australia.
*Corresponding author: School of Mathematics and Computational Science, Xiangtan University,
Hunan 411105, China. E-mail: yuzuguo@yahoo.com.cn or yuzg@xtu.edu.cn
The mitochondrial genomes have provided much information on the evolution of this organelle and
have been used for phylogenetic reconstruction by various methods with or without sequence
alignment. In this paper, we explore the mitochondrial genomes by means of the chaos game

epresentation (CGR), a tool derived from the chaotic dynamical
systems theory. If the DNA sequence is a random collection of bases, the CGR will be a uniformly
filled square; on the other hand, any pattern visible in the CGR contains information on the DNA
sequence. First we use the Markov Chain models proposed by Goldman (Nucleic Acids Research, 1993,
Vol. 21, No. 10 2487-2491) to simulate the CGR of mitochondrial genomes. Then a simple
correlation-related distance approach without sequence alignment based on the CGR of mitochondrial
genomes is proposed to analyze the phylogeny of 64 selected vertebrates.
Keywords: Mitochondrial genomes, chaos game representation, Markov Chain model simulation,
vertebrate phylogeny
OR-005
A New Approach
for DNA Sequence Similarity Analysis based on Triplets of Nucleic Acid Bases
Wei Dan1, Jiang Qingshan2,3
1. School of Information Science and
Technology, Xiamen University, Xiamen, 361005, China
2. Chengdu University, Chengdu, 610106, China
3. Software School, Xiamen University, Xiamen, 361005,
China
Similarity analysis of DNA sequences is a basis in Bioinformatics. The
characteristic distribution of
L-tuple reflects the biological information involved in a biological sequence and thus may be used in
DNA sequence similarity analysis. But similarity analysis based on characteristic distribution of
L-tuple is not effective on very conservative sequence comparison. In this paper, a new similarity
measurement approach based on TNAB (triplets of nucleic acid bases) is introduced for DNA sequence
similarity analysis. The new approach can reflect the content feature and positional feature of a DNA
sequence with the frequencies and position of occurrence of TNAB in the sequence. The experimental
results show that the approach based on TNAB is effective on DNA sequence similarity analysis.
Key Words: DNA sequences, Triplets of nucleotide bases, Similarity analysis, L-tuple; Frequency,
Content feature, Positional feature, vector
OR-006
A Proline-based
Neuraminidase Inhibitor: DFT Studies on the Zwitterion Conformation, Stability and
Formation
Zhiwei Yang
a, Gang Yang a, b,
a. Key Laboratory of Forest Plant
Ecology, Ministry of Education, Northeast Forestry University,
Harbin 150040, P. R. China
b. Institute of Theoretical Chemistry,
Shandong University, Jinan 250100, P. R. China
Corresponding author. Tel: +86-451-82192223; Fax: +86-451-82102082;
E-mail:
theobiochem@gmail.com
The designs of potent neuraminidase
(NA) inhibitors are an efficient way to deal with the recent “2009
H1N1” influenza epidemic. In this work, density functional calculations were employed to study the
stability and formation of the zwitterions of 5-[(1R, 2S)-1-(acetylamino)-2methoxy-2-methylpentyl]-4-[(1Z)-
1-propenyl)-(4S, 5R)]-D-proline (BL), a proline-based NA inhibitor.
Compared with proline, the zwitterion stability of BL is enhanced by 1.76 kcal mol-1 due to the
introduction of functional groups. However, the zwitterion of BL will not represent a local minimum
on the potential energy surface until the water molecules increase up to two (n = 2). With the addition
of two and three water molecules, the energy differences between the zwitterions and corresponding
canonical isomers were calculated at 3.13 and -1.54 kcal mol-1, respectively. The zwitterions of BL are

mainly stabilized by the H-bonds from water molecules, especially in the case of three water molecules
where the carboxyl O atoms are largely coordination-saturated by three H-bonds of medium strengths
and thus make the zwitterion stability even superior to the canonical isomer. With the presence of two
and three water molecules, the energy barriers for the conversion processes from the canonical isomers
to the zwitterions
are equal to 4.96 and 3.13 kcal mol-1, respectively. It indicated that the zwitterion formation is facile to
take place with the addition of two molecules and further facilitated by more water molecules. Besides,
the zwitterion formation of BL is finished in a single step, unlike other NA inhibitors. Owing to the
above advantages, BL is a good candidate of NA inhibitors and more attention should be paid in the
explorations of BL-based drugs.
OR-007
A strategy for parameter estimation for mRNA and protein dynamics
Fortunato Bianconi , Mauro Boccadoro , Gabriele Lillacci , Paolo Valigi
This paper proposes a methodology of parameter identification for nonlinear
systems, in particular
biochemical networks, based on a least squares procedure that treats the signals provided by a high gain
observer. Prior to the estimation phase, identifiability and sensitivity analysis determine which
parameters can and/or should be estimated. The procedure is tested on the data obtained by in silico
experiments for a simple instance of a proposed general dynamic model of protein synthesis.
Keywords: Biochemical Networks, Parameter, Identification, Identifiability , State
OR-008
Mathematical
Platform to Explore Comprehensive Effects of Different Drug Treatments in
Patients with Multiple Myeloma
Yan Wang1, David W. Smith2, Peter Pivonka2
1. Department of Civil & Environmental Engineering,
University of Melbourne, Melbourne, VIC,
Australia
2. Faculty of
Engineering, Computing and Mathematics, University of Western Australia, Perth, WA,
Australia
Multiple Myeloma
(MM) is an incurable but tractable blood cancer, in which over 70% of patients with
MM are involved in bone disease such as bone pain, bone lesions and fracture. Besides widespread
used Bisphosphonates (i.e. Pamidronate), published experimental data indicate that Denosumab, a fully
human monoclonal antibody of RANKL, is very promising in terms of improving bone loss. Recently,
Marathe et al. [1] coupled Denosumab pharmacokinetics in MM patients with bone homoestasishas to
break through ‘black box’ limitations brought by using traditional approach of pharmacodynamics.
However, impacts of MM on bone environment are ignored in the model. Hence, we aim to develop a
MM disease model to be a mathematical platform, based on which comprehensive effects of different
drug treatments in MM patients can be explored pre-clinically and a couple of regimes might be
suggested for clinical trials.
In this study, MM disease model
focuses on examining the impacts of over-expressed RANKL and
DKK1 by MM cells, which exerts their roles through increasing of ratio of RANKL to OPG and
inhibiting activation of Wnt signaling respectively. On the other hand, counteractions of bone
environment on MM cells are also examined in the model, which might be through bone resorption
released TGF-β and over production of IL-6. Being a case study, we integrate the MM disease model
with Denosumab and Pamidronate pharmacokinetics and then optimize the integrated model based on

clinical data [2]. Furthermore, various regimes of Denosumab and Pamidronate including combination
treatments are explored based on the optimized model.
(1). Marathe, A., M.C. Peterson, and D.E. Mager, Integrated Cellular
Bone Homeostasis Model for Denosumab Pharmacodynamics in Multiple
Myeloma Patients. The
Journal of Pharmacology and Experimental Therapeutics, 2008. 326(2): p. 555-562.
⑵. Body, J.‐J., et al., A Study of the Biological Receptor Activator of Nuclear Factor‐KB Ligand
Inhibitor, Denosumab, in Patients with Multiple Myeloma or Bone Metastases from Breast Cancer.
Clin Cancer Res, 2006. 12(4): p. 1221‐1228OR-009
Computational approach towards promoter sequence comparison via TF mapping Using a new
distance measure
Meera A*, Lalitha Rangarajana,
Savithri Bhat1
B.M.S College of Engineering, Bull temple road, Bangalore- 560 019, India
Department of Computer Science, University of Mysore, Mysore, India,
Author for correspondence, Tel : 91-080-26622130, Extn 3029, fax: 91-080-26614357,
Email: savithri.bhat@gmail.com
We propose a method for identifying TFBS in the given Promoter sequence and mapping the
Transcription factors (TFs). The proposed algorithm searches the +1Transcription start site (TSS) for
eukaryotic and prokaryotic sequences individually. The algorithm was tested with sequences from both
eukaryotes and prokaryotes for at least 9 experimentally verified and validated functional TFs in
promoter sequences. The order and type of TF binding to the promoter of genes encoding CMP enzyme
was tabulated. A new similarity measure was devised for scoring the similarity between a pair of
promoter sequences based on the number and order of motifs. Further, these were grouped in clusters
considering the scores between them. The distances between each of the clusters in individual pathway
was calculated and a phylogenetic tree was developed. This method is being further applied to other
pathways such as lipid and amino acid biosynthesis to retrieve and compare experimentally verified
and conserved TFBs.
Keywords: Promoter sequence,
Phylogeny, Database, Central Metabolic Pathway, pattern matching,
Transcription factors (TFs), Transcription factor binding sites(TFBS), similarity measure, Cluster.
OR-010
MultiScale Modeling of Immunotoxin Efficacies in Vascular Tumors
Kevin C. Chen , and Liang Li
Shantou University, Shantou, Guangdong,
515063, China
One of the major setbacks in cancer chemotherapy is the inability
to distinguish malignant cells from
normal ones. Consequently, any anticancer therapy that can target only malignant cells would be a
significant improvement. The use of recombinant immunotoxins (RITs) to target antigens uniquely or
overwhelmingly expressed on cancer cells has become a promising strategy. Based on our previous
work [1], in this study we applid modeling approach to explore the effects of various physiological and
biological functions of RITs on their antitumor efficacies. Specifically, we included the neogenesis and
destruction of tumor vasculatires in our simulations to study their correlations with tumor growth and
resistance to anticancer drugs. We studied different RITs based on Pseudomonas exotoxin (PE) -fused
recombinaant proteins (Fig. 1). In order to incorporate spatial heterogeneity and increased biological
realism, we employed a more computationally challenging scheme based on cellular automata (CA)
called the Cellular Potts Model (CPM) which allows us to treat cells as autonomous agents and to
construct rules based on the local microenvironment (e.g., see [3]). The original Potts model [4],

generalized by Glazier and Graner [5] for biological modeling, has been widely applied to model
differential adhesion and morphogenesis [6-8]. The CPM allows us to describe irregular cell shapes,
since unlike many other CA models, each biological cell is treated as a collection of connected
automata.
In our model,
space was fragmented into a uniform 3D grid composed of identical square elements
(automata). A given element may represent ECS, or a part of a cell or blood vessel as shown in Figure
2. It was correspondingly assigned a type-index, t={e, c, v}. Contiguous elements making up a
biological cell, were assigned a unique cell identity number, s={1, 2, 3…N}, where N is the total
number of cells in the system at a given instant. Further, four state variables were
assigned to each biological cell, (i) the state of RIT intoxication (unaffected or affected),
(ii) the
concentration of receptors on the cell surface [Re] and (iii) in the cytoplasm [Ri], and (iv) the age of the
cell. The interaction between an element and each of its 8 neighbors was characterized by a “free
energy of interaction” J. For example, Jc,c relates (inversely) to the strength of the adhesion between
different cells. Large values of J indicate weak adhesion, and hence enhanced cell migration. To keep
the size of cells fairly constant, we introduced a Lagrangian constraint into the expression for the total
energy E. To study the evolution of the system, we used a standard Metropolis MC method. In the first
stage of modeling, we assumed that the blood vessel elements do not evolve. Thus we selected a site at
a cell-cell or a cell-ECS interface randomly, and proposed a trial move that involves reassigning its
type-index to that of one its neighbors. The change in total energy, DE, was calculated and the trial was
accepted with a Boltzmann probability p=max{1, exp(-DE/T)}, where T is a parameter that controls the
amplitude of the cytoskeletally driven membrane fluctuations.
The division and growth of cells using the CPM resembles previously
reported methodologies [9,10],
in which the age of a tumor cell is compared with the distribution of cell cycle times, and the cell is
divided into two daughter cells if appropriate. The distribution of cell cycle times ensures that all the
cells do not attempt to divide at the same time. The constraint on cell size ensures that the daughter
cells grow to the target cell size As. Similarly, cell death upon RIT intoxication was modeled by setting
the target cell size to zero. The parameters l, and As were estimated from cell size distribution data in a
histological cross section. The parameters J and T can be estimated by examining the density and
motility of cells.
The problem has three
widely separated timescales, tRIT

[3] Alber MS, Kiskowskii MA, Glazier JA, Jiang Y, http://citeseer.ist.psu.edu/, 2004
[4] Potts RB, Proc. Cambridge. Phil. Soc.,. 1952, 48, 106-109.
[5] Graner F, Glazier JA, Phys. Rev. Lett., 1992, 69, 2013-2016.
[6] Glazier JA, Graner F, Phys. Rev. E., 1993, 47, 2128-2154.
[7] Hogeweg P, Artificial Life, 2000, 6, 611-648.
[8] Rappel WJ, Nicol A, Sarkissian A, Levine H, Loomis
WF, Phys. Rev. Lett., 1999, 83, 1247-1250.
[9] Stott EL, Britton NF, Glazier JA, Zajac M, Math. Comput. Model, 1999, 30, 183-198.
[10] Zygourakis K, Bizios R, Markenscoff P, Biotechnol. Bioeng., 1991, 38, 459-470.
[11] Maree AFM, Hogeweg P, Proc. Natl. Acad. Sci. U. S. A., 2001, 98, 3879-3883.
OR-011
Protein Diversity
of Rice Mutants Induced in Space Environment
Wei-Hong Lu1,2 Xin-Zhu Wang3 Lu-Wang1 Ye-Qing Sun14
1. Technology, Harbin, China. Email: lwh@hit.edu.cn.
2. Postdoctoral Fluxion Station of Astronautic Engineering,
Harbin Institute of Technology, Harbin,
China.
3. Biochemistry
Department, Imperial College,London, South Kensington Campus, London SW7 2AZ,
UK;
4. Institute
of Environmental Systems Biology, Dalian Maritime University,Dalian, China. Email:
yqsun@hit.edu.cn
To study the characteristics of changes on rice mutants induced in space environment, we analyzed
proteins in leaves and seeds of four rice mutants (two high tillering and two low tillering) in the 8th and
9th generations after a 15 day spaceflight, and compared with their ground controls by reverse phase
liquid chromatography (RPLC). The results showed that the low abundance proteins of leaves in the
peak tillering stage are more likely to be induced compared with their corresponding controls. The
albumin, globulin, and prolamine of the mutant seeds revealed changes when compared with their
controls, and the characteristics of changes in different mutants
were stably inherited in the 8th and 9th generations, suggesting that
they can be used as biomarkers to
identity the mutants induced by spaceflight.
Keywords: space environment, rice mutant, proteomics,
RPLC
OR-012
Pattern formation
controlled by external forcing in a spatial harvesting predator-prey model
Feng Rao, Weiming Wang, Zhibin Li
In this paper, we present a spatial version
of the Ivlev-type predation-di®usion model which contains
external periodic forcing and harvest on prey. From the numerical results, our results show that external
periodic forcing plays a concernful role in the predation-di®usion model with constant harvest.
Keywords: Predator-prey system , Ivlev , External forcing , Pattern
OR-013
Improving Psiblast fold recognition performance through combining consensus sequences and
Support Vector Machine
Ren-Xiang Yan* , Jing Liu, Yi-Min
Tao
Bioinformatics Center, College of Biological
Sciences, China Agricultural University, Beijing 100094,
China
*Corresponding
author
Email: yanrenxiang_cau@yahoo.cn

Profile-profile alignment may be the most sensitive and useful computational resource for identifying
remote homologies and recognizing protein folds. However, profile-profile alignment is usually much
more sophisticated on algorithm and slower on time than sequence-sequence or profile-sequence
alignment. The profile or PSSM (position-specific scoring matrix) can be used to represent the
mutational variability at each sequence position of a protein by using a vector of amino acid
substitution frequencies and it is a much richer encoding of protein sequences. Consensus sequence,
can be considered as the simplified profile, was used early to improve sequence alignment. Recently,
several studies were carried on to improve Psiblast remotely related protein identification performance
by using the alignment between Psiblast profile and consensus sequences (profile-consensus alignment).
There are several ways can be used to compute consensus residues at each position of a sequence
which capture different information of a profile. Based on this observation, we propose a method that
combined the information of different type of consensus sequences and profiles
with the assistance of support vector machine learning, and results suggest that our
method can further
improve Psiblast fold recognition performance. In addition, we also compared the fold recognition
ability of our method with COMPASS.
Keywords: Psiblast, consensus sequence, profile, SVM
OR-014
Human Oral
Bioavailability Prediction of Four Kinds of Drugs
Aixia Yan Zhi Wang, Meng Meng
Corresponding author phone: +86-10-64421335;
fax: +86-10-64416428;
E-mail: aixia_yan@yahoo.com or yanax@mail.buct.edu.cn
State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering,
P.O. Box 53, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, Beijing 100029,
P. R. China.
In this work, four
quantitative bioavailability prediction models were built for four kinds of drugs using
MLR (Multiple Linear Regression). For the model of Angiotensin Converting Enzyme Inhibitors or
Angiotensin Ⅱ Receptor Antagonists, correlation coefficient r=0.91, MAE (Mean absolute error)
=5.97; for the model of Calcium Channel Blockers, r=0.98, MAE =2.93; for the model of Sodium and
Potasium Channels Blockers, r=0.97, MAE =6.29; and for the model of Quinolone Antimicrobial
Agents, r=0.91, MAE =6.72. Explorations into subsets of compounds were performed and good
quantitative relationship can be built for these four kinds of drugs which were considered have same
pharmacological activity.
Keywords: Human Oral Bioavailability,
Multiple Linear Regression (MLR), Absorption, Distribution,
Metabolism, and Excretion (ADME)
OR-015
Prediction of directly regulated genes of transcription factors important for ascidian early
development
Xuyang Yuan1, 2, Atsushi Kubo3, Yutaka Satou3, Kenta Nakai1, 2, 4
1. Department of Computer Science, Graduate School of Information
Science and Technology,
University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
2. Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai,
Minato-ku, Tokyo 108-8639, Japan.
3. Department of Zoology, Graduate School
of Science, Kyoto University, Kitashirakawa -Oiwake-cho,
Sakyo-ku, Kyoto 606-8502, Japan.

4. Institute for Bioinformatics Research and Development (BIRD), Japan Science and Technology
Agency (JST), Kawaguchi 332-0012, Japan.
The ascidian Ciona intestinalis has been widely
used as a model system to explore gene regulatory
networks in chordate development. Previous systematic gene knockdown experiments highly
contributed to the depiction of a blueprint for ascidian early development. However, limitations of the
experiment itself prevent the blueprint from giving further information regarding direct or indirect
regulation. In this study, we are computationally detecting direct target genes of each transcription
factor by scanning all promoter sequences for its binding site. Taking into consideration the sequence
specificity of TFs, we utilized positional weight matrices, for which suitable threshold values need to
be determined. Given that genes regulated by the same factor share common cis-regulatory elements in
their promoter regions and that those cis-regulatory elements tend to be over-represented, we
introduced an altered over-representation index (ORI) valueto find the optimal threshold that
maximizes the ORI value. For TFs whose binding sites are unknown, we are predicting them by
examination of orthologues to complete the whole network. The direct regulation network of the C.
intestinalis TF ZicL we proposed is consistent with the newly produced data by ChIP-chip experiment.
Once the whole network is finished, it will contribute greatly to our understanding of the precise
molecular mechanisms controlling gene expression during the development of C. intestinalis as well as
vertebrates.
Post-translational
Modification of Phosphorylated KID from Molecular Dynamics Simulation
Hai-Feng Chen*
College of Life Sciences
and Biotechnology, Shanghai Jiaotong University, 800 Dongchuan Road,
Shanghai, 200240, China
E-mail: haifengchen@sjtu.edu.cn Tel: 0086-21-34204348 Fax: 0086-21-34204348
Kinase-inducible domain (KID) as transcriptional activator can stimulate target gene
expression in
signal transduction by associating with KIX. NMR spectra suggest that apo-KID is an unstructured
protein. After post-translational modification of phosphorylation, KID undergoes a transition from
disordered to structured protein upon binding to KIX. The mechanism that folding coupled to binding
is poorly understood. To get an insight into the mechanism, we have performed explicit-solvent
molecular dynamics (MD) for bound and apo-pKID. Room-temperature MD simulations suggest that
pKID becomes more rigid and stable upon KIX binding. Kinetic analysis of high-temperature MD
simulations shows that bound pKID unfolds via a three-state process. Both kinetics and free energy
landscape analyses indicate that bound pKID folds in the order of KIX binding, tertiary folding, helix
αB folding, αA folding, tertiary complete folding, and finally KIX binding. The predicted Φ-values
suggest that there are more key residues in helix αB than in helix αA at TSE. These results are in
qualitative agreement with NMR experiment and can shed light on possible coupling mechanisms
between binding and folding.
Keywords:Transcription factor,
phosphorylation, binding, pKID folding, transition state, Φ-values
Novel protein classifier based on SVM
Georgina Mirceva, Danco Davcev
Faculty of Electrical Engineering and Information Technologies, Skopje, Macedonia
{georgina, etfdav}@feit.ukim.edu.mk
The tertiary structure of a protein molecule
is the main factor which can be used to determine its
chemical properties as well as its function. All information required for a protein to be folded in its

natural structure is coded in its amino acid
sequence. The way this sequence folds in the 3D space are very important, and can be used for
determining protein function. Protein structures are stored in the Protein Data Bank (PDB). With the
rapid growth of technology, the number of determined protein structures increases every day, so,
retrieving structurally similar proteins using current algorithms takes too long (hours or even days). So,
improving the efficiency of protein structure retrieval and classification methods becomes an important
research issue in bioinformatics community.
In this paper, a novel protein classifier is presented.
Our classifier uses the information about the
conformation of protein structures in 3D space. Namely, the voxel based protein descriptor is used for
representing protein structures. The 3D Discrete Fourier Transform is applied to protein tertiary
structures in order to produce geometry based descriptors. Additionally, some properties of the primary
and secondary structure of the protein are considered, thus forming better integrated descriptor.
Part of the SCOP 1.73 database was used for evaluation of our classifier. The results show that
our
approach achieves more than 78.83% classification accuracy and that it is much faster than other
similar algorithms with comparable accuracy. We provide some experimental results.
Keywords: PDB, SCOP, protein classification, Support Vector Machine (SVM).
OR-021
An Association
Test for Multiple Traits Based on the Generalized Kendall’s Tau
Xueqin Wang
Department of Medical
Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University,
Guangzhou 510080, China
In many genetics studies, especially
in the investigation of mental illness and behavioral disorders, it is
common for researchers to collect multiple phenotypes to characterize the complex disease of interest.
It may be advantageous to analyze those phenotypic measurements simultaneously if they share a
similar genetic mechanism. In this study, we present a nonparametric approach to studying multiple
traits together rather than examining each trait separately. Through simulation we compared the
nominal type I error and power of our proposed test to an existing test, i.e., a generalized family-based
association test. The empirical results suggest that our proposed approach is superior to the existing test
in the analysis of ordinal traits. The advantage is demonstrated on a data set concerning alcohol
dependence. In this application, the use of our methods enhanced the signal of the association test.
OR-022
A Series of Studies for Systems Biology of Complex Diseases
Shaoqi Rao,
Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University,
Guangzhou 510080, China
The central theme of biomedical
domians is how to use modern concepts and methods in systems
biology, and high- throughput omics technologies to unravel the underlying genetic mechnisms for
various complex diseases influential on human health, to discover the key genes or interactions, and
finally to develop new methods and technologies for improved medical diagnosis and treatment. In last
five years, the speaker and his associated bioinformatics team have been actively involved in the
frontiers in cardiovascular genetics, statistical genomics and statistics, bioinformatics and systems
biology. This report briefly describes the recent studies undertaken by this team, separated into: (1)
applied

genomical and genetic studies for cardiovascular diseases and other complex diseases; (2)
bioinformatics methods for studying complex diseases; and (3) methodological studies for statistical
genetics and genetic epidemiology. Both lessons and achivements generated from the above studies are
highlighted. Finally, the current research interests and personal prospectives on the future in these
fields are discussed.
OR-023
The spatiotemporal
order of signaling events during Drosophila R8 patterning reveals a robust
pattern of concerted Notch/EGFR signaling for competitive cell fate determination
Zhu, Hao
A fundamental
question in biology is how diverse, complex, robust and accurate developmental
patterning is controlled by limited conserved signaling pathways. To answer this question is important
for deciphering both normal and abnormal signaling. To continuously and simultaneously examine
many signaling events in multiple pathways in experiment during a developmental process is difficult.
With a computational model we investigated both the continuous and discrete aspects of the
Atonal-coordinated Hh, EGFR, Notch and Dpp signaling during Drosophila photoreceptor 8 (R8)
patterning, computing molecular concentrations with differential equations and capturing defined
signaling events in each and every cell. We found that the long-range inductive (proneural) Hh
signaling and the short-range restrictive (antineural) Notch and EGFR signaling form the core system
required for the dynamic patterning of the hexagonal R8 array. Captured signaling events clearly
elucidate molecular concentration changes and cell fate determination processes. The spatiotemporal
order of these events reveals a robust pattern of Notch/EGFR signaling in conducting concerted lateral
inhibition for competitive R8 determination, which is conserved in all correct R8 patterning but
violated in all wrong ones. Moreover, R8 patterning is highly robust against changes in those events
not in the pattern. We hypothesize that such pattern may spatiotemporally determine signaling among
cells via correct interaction among pathways, somewhat similar to the signaling protocols for wireless
and wired communication.
OR-024
Applications
of Chemoinformatics in Systems Biology
Yuhui Wang, Fucheng Zhu, Ying Huang, Liang Feng, Wei Xie, Jianhua YAO*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling
Road, 200032,
Shanghai, China, yaojh@mail.sioc.ac.cn
Systems biology is a biology-based inter-disciplinary
study field that focuses on the systematic study of
complex interactions in biological systems. One of its goals is to discover new emergent properties that
may arise from the systemic view used by this discipline in order to understand better the entirety of
processes that happen in a biological system [1].
Chemoinformatics is the application of informatics methods to solve chemical problems [2]. In
principle, its methods and technologies include data-based, logic-based and principle-based. It can be
applied in all domains which relate to chemicals, i.e. Drug Discovery, TCM Modernization, Food
Safety and etc.
Metabolites in a metabolic pathway are focused in systems biology. In order to study interaction
mechanics between a drug compound and a target, it is necessary and important to study
metabolism of drug compounds in body. Actually, a metabolism procedure of a compound can be
presented as several chemical reactions [3‐5] (Fig.1). Herein, studies of analysis of metabolism

information will be presented. Assisted-Hopping Mechanism for Protein-DNA Binding in
Sox2-Oct1-Hoxb1 Ternary Complex Evidenced from Molecular Dynamics Simulations
Peng Lian1,2, Limin Angela Liu2, Yongxiang Shi1*, Yuxiang Bu1*, Dongqing Wei2*
1 School of Life Science and Institute of Theoretical Chemistry, Shandong University, Jinan, P. R.
China, 250100
2 Department of
Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology,
Shanghai Jiao Tong University, Shanghai, P. R. China, 200240
* Correspondence: shiyx@sdu.edu.cn, byx@sdu.edu.cn, dqwei@sjtu.edu.cn
The “sliding” model or the “hopping” model encapsulates the essential protein-DNA
binding process
for binary complex formation and dissociation. However, the effects of a cofactor protein on such
protein-DNA binding process which lead to the formation of ternary complex remain largely unknown.
Here we investigate the effect of the cofactor Sox2 on the binding and unbinding of Oct1 with the
Hoxb1 control element, and simulate the association of Oct1 with Sox2-Hoxb1 using molecular
dynamics simulations as well as the dissociation of Oct1 from Sox2-Hoxb1 using steered molecular
dynamics simulations, in analogy to a “hopping” event of Oct1. After comparing the kinetic and
thermodynamic properties of three model complexes, we largely abolished the Oct1-DNA base specific
interactions and the Sox2-Oct1 protein-protein interactions in the wild type and two mutants. The
results show that the Oct1-DNA base specific interactions contribute significantly to the total
interaction energy of the ternary complex while the non-specific Oct1-DNA interactions are sufficient
in driving the formation of the protein-DNA interface. The Sox2-Oct1 protein-protein binding interface,
which promotes the formation of the ternary complex and slows the dissociation of Oct1 from its
DNA-binding site, is largely hydrophobic with remarkable shape complementarity. Thus we propose a
simple two step reaction model called an “assisted-hopping” model of protein-DNA binding explaining
the importance ofthe cofactor Sox2 and may apply to similar ternary protein-DNA complexes.
Keywords:Sox2-Oct1-Hoxb1 ternary protein-DNA complex, Protein-protein interactions, Protein- DNA
interactions, Sliding model, Hopping model, Steered molecular dynamics simulations
Fitting
Evolutionary Process of Influenza A Virus Nucleoproteins Using Analytical Solution of
Differential Equation
Shaomin Yan1, Guang Wu2
1National Engineering Research
Center for Non-food Biorefinery, Guangxi Academy of Sciences, 98
Daling Road, Nanning, Guangxi, 530007, China,
2Computational Mutation Project, DreamSciTech Consulting, 301, Building 12, Nanyou A-zone,
Jiannan Road, Shenzhen, Guangdong, 518054, China
The swine A/H1N1 pandemic is threatening our world so
it is important to understand the evolution of
influenza virus in order to better predict new mutations and manufacture effective vaccines. The
nucleoprotein of
influenza A virus plays
critical roles in virus infection and is one of key determinants of host range. In
this study, we use the amino-acid pair predictability to quantify 1709 nucleoproteins isolated from 1918
to 2008 in order to represent the evolution of nucleoprotein family, then we use the system of
differential equations to describe this evolutionary process, and finally we use the analytical solution of
system of differential equations to fit the evolution of the nucleoprotein family. The results show that
the analytica solution can fit the nucleoprotein evolution and the obtained parameters are
useful for the prediction of future mutations.

Key words: Amino-Acid Pair Predictability, Differential Equation, Evolution, Fitting, Influenza A
Virus, Nucleoprotein
A Novel Algorithm for Minimum Recombinant Haplotyping on Pedigrees by Zero Recombinant
Block Partition
Haitao Jiang Yun Xu
Yuzhong Zhao Guoliang Chen
Haplotype inference based on pedigree data under the Mendelian law of inheritance and the minimum
recombination principle is imperative for the construction of haplotype maps and the study of disease
genes. But this problem has been proven to be NP-hard, exact algorithms previously known can't be
applied to handle large scale genotype datasets while heuristic algorithms can't gain high accuracy.This
paper presents an algorithm named Zero recombinant block algorithm (ZRBA) based on a new strategy
using zero recombinant blocks (ZRB) as intermediate structure to reconstruct the haplotype
configurations, theoretical analysis shows that thisstrategy can reduce the possible haplotype
configurations exponentially, and following experiments demonstrate that our algorithm runs much
faster than existing exacthaplotyping algorithms with comparable accuracy.
Key words: haplotyping, pedigree, recombination, zero recombinant block.
Four
long-chain acyl-coenzyme A synthetase genes that might be involved in the biosynthesis of lipids
in Brassica napus
Fuge Zhu , Xiaoli Tan*,
Juan Li , Mingyu Wei, Lili Yu
Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu,
212013, P. R. China.
*Corresponding author: Xiaoli Tan.
Institute of Life Sciences, Jiangsu University,
301 Xuefu Rd, Zhenjiang, Jiangsu. 212013, P.R.China
Long chain acyl-coenzyme A synthetases (LACSs) activate free fatty acid to acyl-CoA thioesters, and
play important roles in the biosynthesis and degradation of lipids. In this study, Four cDNAs encode
long chain fatty acyl-CoA synthetase activity has been found in Brassica napus. Sequence analysis
indicated that the four LACSs possessed typical molecular characteristics of LACS. Compared with
low oil content varieties seed, the four genes is strongly expressed in high oil content varieties seeds at
35 days after pollination (DAP). The expression pattern suggested that the four LACSs might be
involved in the biosynthesis of lipids and oil accumulation in rapeseed.
Keywords: Brassica napus, LACS, sequence analysis, RT-PCR
Classification
models of estrogen receptor-β ligands based on PSO-Adaboost-SVM
Zhengjun Cheng, Yuntao Zhang*, Changhong Zhou, Wenjun Zhang, Shibo Gao
Institute of Applied Chemistry, China West Normal University, Nanchong Sichuan 637002,
China
A new QSAR model for the classification of 135 estrogen receptor-β (ERβ) selective ligands has been
developed with adaptive boosting (Adaboost). The selection of variables for each descriptor was
performed with particle swarm optimization (PSO). Among all descriptors in the model, the RDF
descriptor exhibited the highest accuracy in the predictions. On a known compound data set, the
AdaBoost model improved the prediction accuracy of the training set and the test set to 100.0% and
94.3%, up from 98.0% and 91.4% when only SVM was applied.
Keywords: classification, Estrogen receptor-β, RDF descriptor, particle
swarm optimization, adaptive
boosting, SVM, QSAR model, prediction accuracy

Seasonal trade-off between water- and nitrogen-use efficiency of constructive plants in desert
riparian forest in hyperarid region of China
Shengkui Cao1 Qi Feng,2 Jianhua Si2, Yonghong Su2, Zongqiang Chang2, Haiyang Xi2
1.Division of Hydrology and Water-land Resources in Cold and Arid regions, Cold and Arid
Regions
Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lan Zhou 730000;
Biological and Geographical Sciences Institute , the Qinghai Normal University, XiNing, 810008 china
2.Division of Hydrology and Water-land Resources in Cold and Arid regions, Cold and Arid Regions
Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lan Zhou, 730000
china
E-mail: shkc@lzb.ac.cn
Foliar δ13C values were used
to denote the long-term water use efficiency (WUE) of plants whereas
long-term nitrogen use efficiency (NUE) was estimated by the ratio of C to N. Seasonal variations of
δ13C values, foliar nitrogen concentrations and C/N ratios of P.euphratica and T.ramosissima grown
under five different plots of Ejina desert riparianoasis of northwestern arid regions in china were
studied. The results indicated that T.ramosissima had higher δ13C values, with the mean values of
±
-26.66 0.12‰ compared with P.euphratica. The N concentrations and C/N ratios of two species were
not significantly different. The seasonal pattern of three indexes in two species was similar. The δ13C
values and N concentrations were decreased with the growth period advancing. But the change of C/N
ratios was decline. Among plots, there were higher δ13C values and N concentrations as well as lower
C/N ratios in the Dune and Gobi. Foliar δ13C values were significantly and positively correlated with
N concentrations in P.euphratica and T.ramosissima, whereas significantly negative correlation between
δ13C values and C/N ratios was found for P.euphratica, this relation in T.ramosissima was weak, but
there was significantly quadratic curve relationship between δ13C values and C/N ratios, revealed that
there was a trade-off between WUE and NUE for P.euphratica and in natural condition, which
P.euphratica could not improve WUE and NUE simultaneously. The cost of a high WUE was a low
NUE, and vice versa. But the T.ramosissima could simultaneously enhance WUE and NUE. Those
reflected the different adaptations of desert species to environmental condition.
Design
of PID Controller Based on DNA Computing
Huang Yourui, Tian Yiming, Yin Zhixiang
Anhui University of Science and Technology Huainan 232001, China
hyr628@163.com
The biological Deoxyribonucleic acid (DNA) strand is found to be a promising computing unit.
DNA computing is attracted as one method which gives us suitable answers for optimization
problems. Proportional Integral Derivative (PID) control schemes have been widely used in
industrial fields. Since the PID parameters have a great influence on the stability and
performance of the control system, many approaches have been proposed to determine them.In
this article, we propose double helix structured DNA algorithms to design the type of PID
controller and optimize the PID parameters. The structure of DNA computing is provided, it is
applied into the optimal design of PID controller system. A computer simulation shows that we
can get satisfactoty results with the proposed methodMolecular cloning, characterization and
expression analysis of 3-hydroxy-3-methylglutoryl-Coenzyme A reductase (HMGR) from Panax
ginseng

ChunXi Hou ShouJing Zhao* ,Jian Xue, Lixin Xu, XiaoYan Wu, HuiYun Du.
College of Biological and Agricultural Engineering,Jilin University
Changchun 130022, China
Correspondence author: Shoujing
Zhao
E-mail:swgc@jlu.edu.cn
Pnanx ginseng is an oriental herbal possessing ginsenosides as its main
bioactivity component, having many pharmacological effects, Including immune
system modulation,
antistress activities, antihyperglycemic activities, anti-inflammatory activities, and so on. Ginsenosides
biosynthesis is achieved through a sequence of catalysis and modification in MVA pathway. A partial
length Cdna encoding 3-hydroxy-3-methylglutoryl-Coenzyme A reductase (HMGR; GenBank
Accession NO. GQ455990), which catalyzes the first committed step of isoprenoids biosynthesis
inMVA pathway, was isolated from young leaves of Panax ginseng. The partial cDNA of HMGR
was 360 bp containing a ORF encoding 120amino acids .Database seatches exhibited that PGHMGR
shows identification to Bupleurum chinense HMGR(88%), Picrorhiza kurrooa HMGR(84%)and
Hevea brasiliensisHMGR(82%). These sequences provide a strong evolutionary conservation to
maintain amino acid residues at specific positions, indicating that the conserved
motifs might play important roles in the catalytic properties of the enzyme. Southern
blot analysis
indicated that at one or two copies of PGHMGR gene existed in Panax ginseng genome. Tissue
expression analysis revealed that PGHMGR expressed more strongly in roots than in stems and
leaves.In panax ginseng root explants,HMGR mRNA increased in response to wounding, but was
suppressed treated by
methyl jasmonat�e (MeJA),
in agreement with some previous reports[1-8]. This study showed the Panax
ginseng HMGR gene was differentially expressed in various tissues under different physiological
conditions, which may contribute to the regulation of ginsenodedes synthesis in ginseng species.
Key words: Panax ginseng, hmgr, HMG-CoA reductase, cloning, ginsenosides, biosynthesis
�Thermodynamic
constraints and model reduction for signal transduction networks
Holger Conzelmann, Michael Ederer and Ernst Dieter Gilles
Max-Planck-Institute for Complex Technical Systems, Magdeburg, Germany
Many signal transduction networks are characterized by a ligand induced formation
of multiprotein
signaling complexes. Due to combinatorial reasons the number of distinguishable species and possible
reactions in these processes is enormous. The dynamics of the underlying complex reaction networks
are strongly restricted by thermodynamic constraints that follow from the principle of detailed balance.
Using common modeling strategies, compliance with thermodynamic constraints requires that kinetic
model parameters fulfill certain mathematical restrictions given by the Wegscheider condition. A
violation of the Wegscheider condition corresponds to a violation of the law of energy conservation.
Systematic analyses reveal that these constraints have a descriptive interpretation for multi-domain
proteins. They restrict possible interactions between distinct binding domains. A detailed analysis of
these restrictions also facilitates considerable model reductions. The developed reduction approach
allows us to reduce a detailed model of EGF and insulin receptor cross-talk consisting of over five
thousand
ordinary differential
equations (ODEs) to a size of only 41 ODEs.
Theoretical study of two-photon absorption property of chromophore consisting in green

fluorescent
protein
ng, W.-D. Cheng*
a
M.-Y. Zhang, J.-Y. Wa
State Key Laboratory of Structural Chemistry,
Fujian Institute of Research on the Structure of Matter,
Chinese Academy of Sciences, Yangqiao Street, Fuzhou 350002,China
Green fluorescent protein (GFP) has been shown to be a good flurophore for
two-photon excitation,
readily excited by 780- to 800-nm laser pulses.
n
ate
second
1-3
The two-photon absorption cross section of GFP is
usually obtained by chemically synthesized chromophore compound previously, which did not
consider the protein environment influence. This kind of chromphore is close to planar, but whe
protein matrix exist, chrompore would be exerted some strain away from planarity. Here we calcul
the two-photon absorption properties of cis-trans isomerization of the chromphore. And then through
rotating the exocyclic double bond to breakout the planarity as complements of the protein matrix
effect, we calculate the two-photon absorption cross section of GFP at differently rotate angles. We
further show that, GFP has great intrinsic two-photon absorption cross section when no restrict to
planar structure, as Sean et al. reported by considering the larger protein structure. 1
Two-photon absorption cross section δ is directly related to the imaginary part of the
hyperpolarizability (;,,)γωωωω−− as follow
242203()Im[(;,,)]2Lncωδωγωωωωε=−h
γ ─── third-order molecular polarizability,
0ε ─── the vacuum electric permittivity,
L ─── the local-field factor ─── the refractive index of the medium.
JFeature:
A Java package for extracting global sequence features from proteins for functional
classification
X. Chen1,* and H.Y. Xu1,
1Department of bioinformatics,College
of Life Sciences, Zhejiang University, P.R.China.
*To whom correspondence shall be addressed. Email: xinchen@zju.edu.cn
Both authors made equal contributions.
Conflict of Interest: none declared
Prediction of various functional aspects
of proteins has long been a central theme of bioinformatics in
the post-genomic era. Statistical learning, in addition to analysis based on similarity, was proven
successful to detect complex sequence-function associations in many applications. We present JFeature
as an integrated Java tool to facilitate extraction of global sequence features and preparation of example
sets for statistical learning studies of sequence-function relationships. With a friendly graphical
interface, it computes the composition, distribution, transition and auto-correlation features from
sequences, as well as helps to assemble a negative example set based on the most-dissimilar principle.
The Java package and supplementary documentations are available at
http://www.cls.zju.edu.cn/rlibs/software/jfeature.html.
Keywords: Machine Learning, Feature Extraction, Java Package,
Software, Protein Sequence Codin.
PO-009
Size Effect on Protein Encapsulation in Carbon Nanotubes
Lijun Liang, Qi Wang, Tao Wu, Yu Kang
Department of Chemistry, Zhejiang University,
Hangzhou 310027, P. R. China
Recently, the ability of CNTs to serve as biocompatible transporters for drug delivery
has aroused great
expectation. Based on the exciting potentials, we try to focus on the spontaneous phenomenon of the

protein encapsulated in CNTs by molecular dynamics (MD) simulations. Here we mainly explore the
importance of the diameter selectivity a spontaneous encapsulation of a model protein in the CNT. The
investigated globular protein was observed to enter the CNT with a suitable size. If the CNT grows
larger, the protein seems not to enter the CNT actively with the limited time scale. While the CNT gets
smaller, the protein was jammed partially in the tube mouth although there is enough space in the
cavity of the CNT to fit the protein. By plotting the free energy change in this process, the energy
barrier was observed. To the spontaneous insertion process, the suitable diameter of the CNT tends to
be a key factor. The overlarge CNT makes it difficult because of the insufficient protein-CNT van der
Waals attraction, whereas too small a CNT hinders the process due to the resistance from destroying
hydrogen-bond networks of the solvent and the conformational entropy loss of the protein.
Figure 1. Free energy changes of the encapsulation process in CNTs with different sizes via Potential
of Mean Force (PMF) calculation.
PO-010
Root water
uptake model of Populus euphratica in desert riparian forest in extreme arid region
Tian Yongzheng
Research Institute, Chinese Academy of
ous Region , Bayanhot
uthor: Si Jianhua, Ph. D, mainly engaged in eco-hydrology and water resources in
000,
to transfer soil water to the atmosphere,it is an important part of
l, root density , soil
ecture for Multi-class Protein Folds Classification
gineering, Xiangtan University, Hunan, 411105, China
1,2
Si Jianhua1 *
Feng Qi 1
, Cao Shengkui 1
1. Cold and Arid Region Environmental and Engineering
Sciences. No. 320 Donggang West Road, Lanzhou 730000, P. R. China;
2. Research Institute of Forestry, Alxa League of Inner Mongolia Autonom
750306 , China
* Corresponding a
arid regions, address: Division of Hydrology and Water-land Resources, Cold and Arid Regions
Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lan Zhou 730
China. E-mail: jianhuas@lzb.ac.cn
Plant root water uptake is a key way
the research on water transforming patterns in the SPAC. So understanding the water absorption
patterns of plant root system is a base to recognize the SPAC. Recently there are many papers dealing
with the studies of the water absorption patterns of plant root system but the researched plants are
mostly focused on crops and the main researched areas are the regions with adequate precipitation.
There are only a few studies dealing with the water absorption of natural plants in extreme arid desert
regions. This paper studied the root water absorption patterns of Populus euphratica and established the
corresponding mathematical model based on the data of root density and soil water dynamics in root
zone in desert riparian forest in extreme arid region.The finite difference method was used to discrete
the soil water movement equation with evaporation boundary conditions, and the procedure of the
numerical simulation of the model was programmed. The results of numerical simulation analysis of
soil water movement in root zone of Populus euphratica showed that the simulation values were
consistent well with the measurement values with a precision ranging between 92% and 98%. This
work provides a theoretical basis for the study of water movement in the SPAC.
Keywords: desert riparian forest, Populus euphratica, root water uptake mode
moisture ,extreme arid region.
A Two-layer Learning Archit
Ruofei Wang 1
, Xieping Gao 2
1,2.College of Information En
1. Email: wrf0694@gmail.com

2. Email: xpgao@xtu.edu.cn
Classification of protein folds plays a very important role in the protein structure discovery process,
especially when traditional sequence alignment fail to yield convincing structural homologies. In this
paper, we have developed a two-layer learning architecture, named TTLA, for multi-class protein folds
classification. In the first layer, OET-KNN (Optimized Evidence-Theoretic K Nearest Neighbors) was
used as the component classifier to find the most probable K-folds of the query protein. In the second
layer, we use support vector machine (SVM) to build the multi-class classifier just on the K-folds,
generated in the first layer, rather than on all 27 folds. For multi-feature combination, ensemble
strategy based on voting is selected to give the final classification result. The standard percentage
accuracy ~63% is achieved on the independent testing dataset, where most of the proteins have

Guowen Xie 1
, Meizhen Lin 2
, Yisheng Zheng 1
, Yanlin Zheng 1
, Xiaoyu Peng 1
1. School of Life Science, Guangzhou University, Guangdong, Guangzhou 510006,
China;
2. College of Geographical Science, Guangzhou University, Guangdong, Guangzhou 510006,
China
Monimopetalum chinense (Celastraceae) is a rare, endemic and clonal plant in China. In the present
study, genetic differentiation and clonal diversity of Monimopetalum chinense populations were
studied using inter simple sequence repeat ( ISSR ) markers. According to the results, the effective
conservation measures were produced. The results indicated that the population has high clonal
diversity ( D = 0.9969 ). In addition, there was great clonal differentiation among populations with no
the widespread genotyes. The level of genetic variation at species level or at population level are all
lower( species level: PPB = 39.2%, HT = 0.129; Populations level: PPB = 15.64%, HS = 0.0557 )than
that most of clonal plant. Strong genetic differentiation among populations was detected in
Monimopetalum chinense, with 49.06% of total genetic variation ( AMOVA ), 0.5672 of Nei's gene
differentiation coefficient ( GST ) and 0.5464 of Shannon information index. The population
fragmentation since the end of Tertiary period, genetic drift of small population size and the form of
inbreeding reproduction would have contributed to such genetic differentiation among populations of
Monimopetalum chinense. Based on these findings, it was suggested that these populations with
relatively high genetic diversity should be protected in situ, and adopted introduction among
populations for this species, so that the genetic diversity of Monimopetalum chinense should be
conservated effectively.
Key words: Monimopetalum
chinense, population, ISSR, genetic differentiation, clonal diversity
PO-015
Using Adaptive
K-nearest Neighbor Algorithm and Cellular Automata Images to Predicting
G-Protein-Coupled Receptor Classes
Xuan Xiao and Wang-ren Qiu
Computer Department , Jing-De-Zhen
Ceramic Institute, Jing-De-Zhen 33300, China
G-Protein-Coupled Receptor (GPCRs) are the largest of cell surface receptor, accounting
for >1% of
the human genome. They play a key role in cellular signaling networks that regulate various
physiological processes. The functions of many of GPCRs are unknown, because they are difficult to
crystallize and most of them will not dissolve in normal solvents. This difficulty has motivated and
challenged the development of a computational method which can predict the classification of the
families and subfamilies of GPCRs based on their primary sequence so as to help us classify drugs. In
this paper the adaptive K-nearest neighbor algorithm and protein cellular automata image (CAI) is
introduced. Based on the CAI, the complexity measure factors derived from each of the protein
sequences concerned are adopted for its Pseudo amino acid composition. GPCRs were categorized into
nine subtypes. The overall success rate in identifying GPCRs among their nine family classes was
about 83.5%. The high success rate suggests that the adaptive k-nearest neighbor algorithm and protein
CAI holds very high potential to become a useful tool for understanding the actions of drugs that target
GPCRs and designing new medications with fewer side effects and greater efficacy
PO-016
Evaluation of Coupled Nuclear and Cytoplasmic p53 Dynamics
Tingzhe Sun, Jun Cui, Meihong Cai and Pingping Shen*
State Key Laboratory of Pharmaceutical Biotechnology, School
of Life Sciences, Nanjing University,
Nanjing, 210093, People’s Republic of China.

* To whom correspondence should be addressed
Fax: 86-25-83594060 Email: ppshen@nju.edu.cn
Conflict of Interest: The authors declare no conflict of interest.
The tumor suppressor p53 predominantly serves as a sequence
specific transcription factor and
becomes activated upon exposure to diverse stimuli. One potent death inducer PUMA, is
transcriptionally induced by p53. Once released into cytoplasm, it can lead to the activation of Bcl-2
apoptotic network. The cytoplasmic proapoptotic roles of p53 have recently been discovered, which
engage p53 into the chemical interactions with Bcl-2 family members. PUMA can also relieve p53
from the sequestration of antiapoptotic members. Released p53 further enters nucleus and induce
PUMA expression. We proposed that this positive feedback loop can elicit inherent bistability. Further
sensitivity analysis suggested that this system is considerably sensitive to p53 production rate and
downstream effectors are much more affected by sensitive parameters than upstream effectors. Thus,
this newly discovered positive feedback loop might play critical roles in apoptotic network.
Key words: p53, cytoplasm, nuclear, PUMA, bistability, stochastic simulation, local sensitivity, Monte
Carlo
PO-017
The Study of Transesophageal Oxygen Saturation Monitoring
Zhiqiang ZHANG, Bo GAO*, Guojie LIAO, Ling MU, Wei WEI
In this study, transesophageal oxygen saturation (SpO2) monitoring system was established based on
early experiments, to provide a new program of SpO2 acquisition and analysis, and avoid the limitation
of traditional methods. The PPG signal of descending aorta and left ventricular was monitored in the
experiment. The analysis of peak-to-peak value, standard deviation and position of peak in signal
waveform showed that in vivo signal was more stable and sensitive; the physiological information was
reflected in the left ventricular PPG waveform. Therefore, it can be concluded that transesophageal
SpO2 monitoring technology had a better guide in clinical application.
Key words : esophagus, SpO , PPG, left ventricle, descending aorta, standard
deviation, peak-to-peak
2
value
PO-018
Topological
analysis of axon guidance network for Homo sapiens
Chen Xu-ning, Zhu Wei-ping
Shanghai Institute of Applied Mathematics and Mechanics, Shanghai University, Shanghai 200072,
China
Axonal outgrowth is usually guided by a variety of guidance factors, such as netrins, ephrins, slits
and semaphorins, andis one of the critical steps for the proper formation of neural networks. However,
in this stage how the signal molecules function and why some of these play more important roles than
the others in guiding the axonal directional outgrowth has not been answered clearly. In this study, we
try to solve the problem by using the complex network analysis method. The signal molecules and
interacts are treated as the nodes and edges to construct the axon guidance network model for Homo
sapiens. The data of the model are taken from the KEGG database, and an analysis workbench named
Integrative Visual Analysis Tool for Biological Networks and Pathways (VisANT) is employed to
analyze the topological properties, including the degree distribution and the top co-expressed genes of
the axon guidance network. This study has just opened a window onto understanding the mechanism of
the axon guidance.
Key Words: axon guidance,
complex networks, topological properties

PO-019
Evaluating Post-translational Modification Identification by InspecT
Hong Li1,2, Sujun Li2, Qingrun Li2, Rong Zeng2, Yu Shyr3, Lu Xie1§
1. Shanghai Center for Bioinformation Technology, 100 Qinzhou Road, Shanghai
200235, P.R.China
2. Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of
Sciences, 320 Yueyang Road, Shanghai 200031, P.R. China
er, Nashville, TN, USA
c.cn SJL: sjli@sibs.ac.cn QRL: qrli@sibs.ac.cn
g
scale is important, due to the
slational modifications, InspecT, evaluation, proteomics, machine learning
form microarray data integration combining meta-analysis andgene set enrichment
2, 1*,
Jian Yu Miaoxin Li 1,
Yajun Yi 3
, Yu Shyr 3
, Yixue Li 1
, 2 §
, Lu Xie1 §
3. Cancer Biostatistics Center, Vanderbilt-Ingram Cancer Cent
§Corresponding author: xielu@scbit.org
Email addresses:
HL: lihong@sibs.a
RZ: zr@sibs.ac.cn YS: yu.shyr@vanderbilt.edu LX: xielu@scbit.or
Understanding post-translational modifications (PTMs) on a proteomic
universal and complex functions of PTMs; however, reliable and unrestrictive PTM identification is
still one of the biggest challenges in proteomics. InspecT is an algorithm with a broad range of
applications in the identification of PTMs, especially in unrestrictive searching of PTMs. In this paper,
we propose a strategy for evaluating the PTM identification results of InspecT. We employed three
evaluation methods (false discovery rate, principal component analysis, and support vector machine)
on three InspecT search types (unmodified peptides, phosphorylation peptides, and unrestrictive PTM
searching). The proposed evaluation strategy has been implemented as a web server for InspecT users
(http://www.biosino.org/Validation/). Similar approaches can be used to evaluate PTM identification
by other algorithms.
Key Words: post-tran
PO-020
Cross-plat
analysis
Jun Wu1
, USA
*
,
1. Shanghai Center for Bioinformation Technology, 200235 Shanghai, China
2. College of Life Science, Tongji University, 200092 Shanghai, China
3. Cancer Biostatistics Center, Vanderbilt University, 37232 Nashville, TN
*Jun Wu and Jian Yu contributed equally to this work.
§Correspondence to: yxli@scbit.org, or xielu@scbit.org
Email addresses: Jun Wu: wujun@scbit.org
Jian Yu: yujian@scbit.org
Miaoxin Li: limx54@yahoo.com
Yajun Yi: andrew.yi@vanderbilt.edu
Yixue Li: yxli@scbit.org
Lu Xie: xielu@scbit.org
Integrative analysis of microarray
data has always been both fascinating and challenging. Recently,
gene set enrichment analysis (GSEA) has been widely applied to bring gene-level interpretation to
the pathway level; however, GSEA does not allow for integrating multiple original microarray
datasets. The objective of this study is to construct an integrative analysis approach to extract
consistent expression pattern change data from multiple microarray datasets at the pathway level. In
this article, two pipelines were developed. Pipeline I, combining meta-analysis and gene set
enrichment analysis, was established to integrate data from similar microarray platforms. For

analysis across different platforms, we modified the algorithm from an advanced version of GSEA,
analysis of sample set enrichment scores (ASSESS). The modified algorithm (ASSESS’) was
linked to meta-analysis to form Pipeline II for the integration of data from different microarray
platforms. Pipeline I was able to identify 20 changed pathways that could not be identified by
GSEA in single breast cancer datasets; one pathway was validated in another breast cancer dataset.
Pipeline II was able to identify six changed pathways that could not be found based on combining
the GSEA analyses of single liver cancer dataset. Our work provides simple and effective strategies
to integrate multiple gene expression profiles for similar research objects at the pathway level,
which allows pathway ranking analysis based on utilizing a larger sample size. It may also allow
biological system overview based on statistical integration of multiple gene expression studies. A
web server for Pipeline I is available at: http://lifecenter.sgst.cn/pipeline1/home.htm
PO-021
Xie, Lu
PO-022
Sequence-discrimination
by PspGI
Keith D. Lunnen, Elizabeth Lang, and Geoffrey
G. Wilson
New England Biolabs, Inc., 240 County Road, Ipswich, MA 01938,
USA
PspGI is a thermostable restriction enzyme from the archaeon Pyrococcus [1]. PspGI recognizes
the sequence CCWGG in double‐strand DNA, and cleaves before the first C in each strand to
produce fragments with 5‐base, 5’‐overhangs. The crystal structure of PspGI bound to its
recognition sequence has been solved [2]. The enzyme acts as a homodimer, encircling the DNA
and contacting the base pairs in both the major‐ and the minorgrooves. We are investigating the
molecular mechanism by which PspGI discriminates the central base pair of its recognition
sequence. From the crystal structure, discrimination of the C:G base pairs occurs by majorgroove
contacts with the invariant amino acids Arg164, Glu165, and Arg166 of each subunit, but
discrimination of the central base pair—which can be either A:T or T:A (i.e. W:W) but not G:C or
C:G (i.e. not S:S)—is unclear and remains the subject of experimentation [3]. We tested whether
this discrimination occurs passively, by steric clashes in the minor groove. A:T and T:A base pairs
are smaller than G:C and C:G base pairs in the minor groove due to the presence of the 2‐amino
group that protrudes from the ring of Guanine but not from Adenine. If the space in the
DNA‐binding site needed to accommodate this group were occupied by an amino acid instead,
then G:C and C:G would not fit into the site, whereas A:T and T:A would fit. From the crystal
structure, two amino acids that might clash with Guanine in this way were identified: Tyr67 and
Phe97. Each was changed to other amino acids by mutagenesis, and the resulting variant
enzymes were assayed to see if any now cleaved CCSGG in addition to CCWGG. All of the
catalytically active Phe97 mutants examined to date continue to cleave only CCWGG, suggesting
that Phe97 is not involved in sequencediscrimination.The Tyr67 mutants also continue to cleave
only CCWGG, but many now appear to bind—although not to cleave—CCSGG as well,suggesting
that Tyr67 is at leasta factor in sequence-discrimination.
[1] Morgan, R., Xiao, J.-P. and Xu, S.-Y., Appl. Environ. Microbiol. 1998, 64, 3669.
[2] Szczepanowski, R.H., Carpenter, M.A., Czapinska, H., Zaremba, M., Tamulaitis, G., Siksnys, V.,
Bhagwat, A.S. and Bochtler, M., Nucleic Acids Res. 2008, 36, 6109.
[3] Tamulaitis, G., Zaremba, M., Szczepanowski, R.H., Bochtler, M. and Siksnys, V., Nucleic Acids
Res. 2008, 36, 6101.

PO-023
Molecular Dynamics Studies of The Solidβ-HMX: Effects of Hydrostatic Pressure and
Temperature
Shuo Liu1,2, Jing
Chang1,3 and Dong-Qing Wei1
1, College of Life Science and Biotechnology, Shanghai
Jiaotong University, 200240,China
2, Physics Department, Liaoning University, Shenyang, China
3. Institute of Atomic and Molecular Physics, Sichuan University,
Chengdu, 610065, China
The structural, electronic, and mechanical properties of the energetic material β-HMX have
been
studied with the isothermal-isobaric molecular dynamics (NPT-MD) simulation,. The variations of cell
volume, lattice constants of solid β-HMX are presented and discussed at different pressure and
temperature.
Isothermal-isobaric
MD simulations are performed in the temperature range of 5~450K and pressure
range of 0~40GPa. It is found that β-HMX undergoes a phase translation at 360K and 27GPa where
discontuities were observed for the volume and internal geometrical parameters. The N-N bond is
significantly lengthened with increasing temperature, which leads us to believe that it is relevant to the
initial decomposition. There is a larger compression along the c-axis than along the a- and b-axes.
Instead of the COMPASS forcefield used in previous studies[1-4], we tested the applicability of other
two forcefields, i.e. CVFF and PCFF.
References
Lu Lai-Yu, Wei
Dong-Qing, Chen Xiang-Rong, Ji Guang-Fu, Zhang Qing-Ming, Gong Zi-Zheng.The
structural properties of solid β-HMX under compression by the first principle study. Mol. Phys. 2008,
106: 2569
Lu Lai-Yu, Wei Dong-Qing, Chen Xiang-Rong, Ji Guang-Fu, Zhang Qing-Ming, Gong Zi-Zheng. The
Pressure Induced Phase Transition of The Solid β-HMX By The Isothermal-Isobaric Molecular
Dynamics Simulations. Mol. Phys. in press.
Lian Dan, Lu Lai-Yu, Wei Dong-Qing, Zhang
Qing-Ming, Gong Zi-Zheng, Guo Yong-Xin. High
pressure behaviour of β-HMX crystal studied by DFT-LDA. Chin. Phys. Lett. 2008, 25: 899
Lu Lai-Yu, Wei Dong-Qing, Chen Xiang-Rong, Ji Guang-Fu. First-principles calculations of structure
and electronic properties of solid pentaerythritol under pressure. Chin. Phys. Lett. 2008, 25: 3368
PO-024
Molecular dynamics simulations of dipolar fluids in orientationally ordered phases
Lin Gao
1
Co hnology, Shanghai Jiaotong University, China 200240
1,2
and Dong-Qing Wei 1
llege of Life Science and Biotec
2
Physics Department, Liaoning University, Shenyang, China
A recent study shows that the charge separation of dipole particle plays a significant role on the
phase transition of ferroelectric liquid crystal phases. In present paper, molecular dynamics (MD)
simulations were performed for the real dipole model with a reduced distance between the two
charges compared to the previous work, so that it is closer to thepoint dipole model. Much longer
simulations were made compared with earlier work in order to obtain decent results. The potential
energy consists of the site-site Lennard-Jones potential and electrostatic contribution of partial charges.
Results show that chain-like structures in low density regime, nematic, columnar and ferroelectric solid
phase are formed. Detailed analyses were made regarding fluctuation of the order parameters 1p and 2p
as functions of density along with other thermodynamic properties.
References

1.D. Q. Wei and G. N. Patey, Phys. Rev. Lett., 68 , 2043 (1992).
2.D. Q. Wei and G. N. Patey, Phys. Rev. A, 46, 7783 (1992).
3.D. Q. Wei and G. N. Patey, Phys. Rev. E, 47, 506 (1993).
4.D.Q. Wei, Y.J. Wang, L. Wang, J.H. Hu, Z.-Z. Gong, Y.X. Guo, and Y.S. Zhu, Phys. Rev. E 75,
061702 (2007).
PO-025
QSAR analyses
on avian influenza virus neuraminidase inhibitors using CoMFA and CoMSIA
Chaonan Wang, Lu Liu, Jingfang Wang, Jianjun Zhu and DongqingWei
Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai
Jiaotong University, 800 Dongchuan Road, Minhang District Shanghai, 200240, China
Recently , the H5N1 avian influenza virus (AIV) are spreading widely in Asia, Africa and
Europe, its
acute infection of the upper respiratory tract [1 ]and the high rate of causing fatal in human has
improved graven concerns on a pending global flu pandemic. The only treatment or prophylaxis
currently in humans are Neuraminidase (NA) inhibitors. However, The rapid emergence of strong
resistant mutants made the vaccines against influenza virus ineffective and the deficient supply of
synthetic material have limited the applications seriously[2-4]. To design much more useful virus
inhibitors with new structures against the NA, we used autodock, CoMFA, and CoMSIA to investigate
the quantitative structure–activity relationship for 135 NA inhibitors(NIs) with a great structural
diversity against influenza A virus. Based on the binding conformations obtained from molecular
docking with crystal structure of NA, We successfully built up the CoMFA and CoMSIA models with
a high cross-validated q2 respectively. These models also reveal a detail information about how
electrostatic, steric, hydrophobicity, and individual fragments affect the potency of NA inhibitors. In
addition, the field distributions of CoMFA and CoMSIA are found to be well agreement with the
structural characteristics of the binding sites. Therefore, the final 3D-QSAR models and the
information of the inhibitor–enzyme interaction should be of value for designing novel potent NA
inhibitors.
References
1Pennisi, E. Science
270, 1916–1917(1995).
2Mingyue Zheng, Kunqian Yu, Hong Liu, Xiaomin
Luo et al, J Comput Aided Mol Des, 20, 549–566
(2006)
3Jing-Fang
Wang , Dong-Qing Wei*, Kuo-Chen Chou, “Pharmacogenomics and Personalized Use of
Drugs”, Current Topics in Medicinal Chemistry, 8, 1573-1579(2008).
4Dong-Qing Wei, Qi-Shi Du, Hao Sun, Kuo-Chen Chou, “Insights from Modeling the 3D structure of
H5N1 influenza virus neutaminidase and its binding interactions with ligands”, Biochemical and
Biophysical Research Communications, 344 1048 (2006) .
PO-026
Homology modeling and molecular docking study of Cytochrome 4L4 of Cabbage looper
Tao Zhang, Yao Zhou, DongQing WeiDepartment
of Bioinformatics and Biostatistics, School of Life
Science and Biotechnology, Shanghai Jiao Tong University, DongChuan Road 800 , 200240 Shanghai,
China
Cytochrome
P450 enzymes constitute a superfamily of heme-containing enzyme, which are widely
distributed in nature and play an important role in many aspects such as the metabolism of xenobiotics,
detoxification and synthesis of endogenous compounds. In insect, the P450 enzymes mainly participate
in the metabolism of pesticides and insecticides. Recently, a research identified that in cabbage looper

(Trichoplusia, ni) there was a dose and time dependent relationship between the protein express level
of CYP4L4 and concentration of fenvalerate, a potent synthetic pesticide, suggesting that CYP4L4 was
implicated in pesticide metabolism and resistance [1]. In this study a three-dimensional model structure
of CYP4L4 is build based on the CYP4L4 protein sequence of Mamestra brassicae using the
homology modeling method and refined by molecular dynamics simulation. Then the molecular
docking was performed on the model structure and the molecular of fenvalerate. The docking results
show that the molecular of fenvalerate was positioned in the pocket with the side of hydrophobic
residues and another side of hydrophilic residues. In addition, the channel to enter into the pocket of
CYP4L4 was identified in the complex with fenvalerate. According to the conformation of fenvalerate
binding with CYP4L4 predicted by molecular docking, the hydroxylation position of fenvalerate was
close to the heme, the prosthetic group of P450 enzyme, indicating the rationality of the predicted
conformation. These observations provided the atomic-level interpretation how CYP4L4 interacted
with the fenvalerate and the insights into the modification of pesticide to avoid the resistance.
[1] Fang, X., D. Huang, Z. Wang, C. Wan, T. Sun, W. Xu, C. Liu, P. Zhou, and Z. Qiao, Cell Biol
PO-0
and dynamic properties of a new amyloidogenic chicken cystatin mutant I108T
University, 66 Chongshan Zhong Road, 110036 Shenyang, China
variant I108T is a mutant in the hydrophobic core of the molecule. It has shown many
Keyw
[1] Engh, D. Musil, U. Thiele, R. Huber, A.Karshikovl, J. Brzin, J. Kos and V. Turk,
[2] 2000, 7, 70–79.
akami and A. Kato, Protein Sci. 2006, 15,
C. Kutzner, D. van der Spoel and E. Lindahl, J. Chem. Theory Comput. 2008, 4, 435-447.
ng BspQI Nicking Enzymes and Application of N.BspQI in DNA Labeling and
oo 1
, James C. Samuelson 1
, Siu-Hong Chan 1
, Tamas Vincze 1
Toxicol. 2007, 23, 445.
27
Structural
Yuanyuan Yu1, Youtao Song1, 2
1. College of Life Science, Liaoning
2.Province Key Laboratory of Animal Resource and Epidemic Disease Prevention, 110036 Shenyang,
China
Chicken cystatin
amyloid-prone characteristics in our previous experimental study. To explore the detailed
structural and dynamic properties of the amyloidogenic mutant I108T, 10 ns molecular dynamic
simulations of the I108T mutant and wild-type chicken cystatins were performed in this study.
Our results suggested that the I108T mutant, which exhibited larger secondary structural
fluctuations and hydrophobic core expanding tendency compared with the wild-type chicken
cystatin, is a new amyloidogenic form of chicken cystatin, and therefore supported the hypothesis
to some extent that site mutations in the hydrophobic core might induce the domain swapping.
ords: Chicken cystatin, Molecular dynamic simulation, Amyloidosis, hydrophobic core, domain
swapping.
W. Bode, R.
EMBO J. 1988, 7, 2593 – 2599.
I. Olafsson and A. Grubb, Amyloid.
[3] J.W. He, Y.T. Song, N. Ueyama, A. Saito, H. Az
213-222.
[4] B. Hess,
PO-028
Engineeri
Production ofSingle-strand DNA
Penghua Zhang ,
pswich, MA 01938
1
, Priscilla Hiu-Mei T
Stephanie Doucette 1
, Stefan Bäckström 2
, Konstantinos D. Potamousis 3
, Timothy M. Schramm 3
, Dan
Forrest 3
, David C. Schwartz 3
, Shuang-yong Xu1 *
1. New England Biolabs, Inc. 240 County Road, I

2. Göteborg University, Department of Medical Biochemistry and Cell Biology, Medicinaregatan 9A,
Box 440, SE-40530, Göteborg, Sweden
3. Laboratory for Molecular and Computational
Genomics, Department of Chemistry, Laboratory for
Genetics, University of Wisconsin-Madison Biotechnology Center, University of Wisconsin-Madison,
425 Henry Mall, Madison, Wisconsin 53706
Phone: 978-380-7287 Fax: 978-921-1350 Email:
xus@neb.com
BspQI is a thermostable Type IIS restriction endonuclease (REase)
with the recognition sequence 5’
GCTCTTC N1/N4 3’. Here we report the cloning and expression of the bspQIR gene for the BspQI
restriction enzyme in E. coli. Alanine scanning of the BspQI charged residues identified a number of
DNA nicking variants. After sampling combinations of different amino acid substitutions, an Nt.BspQI
triple mutant (E172A/E248A/E255K) was constructed with predominantly top-strand DNA nicking
activity. Furthermore, a triple mutant of BspQI (Nb.BspQI, N235A/K331A/R428A) was engineered to
create a bottom-strand nicking enzyme. In addition, we demonstrated the application of Nt.BspQI in
optical mapping of single DNA molecules. Nt or Nb.BspQI-nicked dsDNA can be further digested by
E. coli exonuclease III to create ssDNA for downstream applications. BspQI contains two potential
catalytic sites: a top-strand catalytic site (Ct) with a D-H-N-K motif found in the HNH endonuclease
family and a bottom-strand catalytic site (Cb) with three scattered Glu residues. BlastP analysis of
proteins in Genbank indicated a putative restriction enzyme with significant amino acid sequence
identity to BspQI from the sequenced bacterial genome Croceibacter atlanticus HTCC2559. This
restriction gene was amplified by PCR and cloned into a T7 expression vector. Restriction mapping
and run-off DNA sequencing of digested products from the partially purified enzyme indicated that it is
an EarI isoschizomer with 6-bp recognition, which we named CatHI (CTCTTC N1/N4).
PO-029
Prediction of Protein Binding Sites with Incremental Convex Hull Algorithm
Jing He and Dong-Qing Wei
Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai
otein surface[1,2].
re
re,
Wang and Dong-Qing, Wei*, “Role of Structural Bioinformatics and TCM databases in
2.Ch hou, Dong-Qing Wei *
Jiaotong University, 800 Dongchuan Road, Minhang District, Shanghai, China
The most potential protein binding sites are some pocket-shaped regions on the pr
Connolly, Brady and Stouten presented a mathematical solution by calculating the positions of a sphe
of given radii tangential to three protein atoms whose radii are not necessarily equal[3]. However, this
algorithm requires O(N
, “Molecular
4
) computational times. As N is the number of protein atoms, it takes extremely
long time for a protein of decent size. An incremental convex hull scheme is introduced to ameliorate
this algorithm. Suppose each convex hull is a three-contacting sphere, one adds protein atoms once at a
time to update the hull similar to incremental algorithm. The computational cost can be reduced to
O(N 2
) as estimated, which is much more efficient compared with the original algorithm. Furthermo
the catalytic features of the enzymes, as well as, the ligand-receptor complex information from the
PDB databank will be used to further improve the precision of prediction.
References:
1. Jing-Fang
Pharmacogenomics”, Pharmacogenomics, 10, Issue 10 (2009).
eng-Cheng Zhang, Jing-Fang Wang, Jing-Yi Yan, Kuo-Chen C
Modeling of CYP Proteins and Its Implication for Personal Drug Design”, in Automation in Genomics
and Proteomics: An Engineering Case-Based Approach Eds Gil Alterovitz, Roseann Benson, Marco
Ramoni,John Wiley, 2009(ISBN: 978-0-470-72723-2).

3.Brady P, Stouten PFW. Fast prediction and visualization of protein binding pockets with PASS. J
Comput Aided Mol Des 2000;14:383–401.
PO-030
An Evolution
Model under Minority Game
Quan Fang1, Jiao Wang2, Wei Zheng2 and Sheng
Li2
1.Department of Bioinformatics and Biostatistics, Shanghai
Jiao Tong University, Shanghai, 200240
China
2.Department
of Physics, Shanghai Jiao Tong University, Shanghai, 200240 China
By making use of minority game theory, we proposed an evolution model of two components
genes.
The strategies of agents attending the minority game were considered as quasispecies of two
components genes. In the model, the strategies mutate randomly with time and the results of minority
game selected which strategies will survive during the evolution. The process accords with the
principle of Darwin’s evolution. Minority game here can be considered as competition of finite
population for limited resources. Numerical stimulations reveal the agents tend to aggregate on some
most popular strategies which means the distribution of the quasispecies is not random but centre
around certain master sequences. Meanwhile the popularity landscape of the strategy pool is evolving
and the master sequences drift with time. Another observation is that the distribution of quasispecies is
power law distribution. No threshold of the probability of mutation was found in this model.
PO-031
Molecular Modeling Studies of CYP 450 And Its Implication For Personalized Medicine —
Metabolizing Mechanism of CYP2E1
Jue Li and Dongqing Wei
Department of Bioinformatics
and Biostatistics, School of Life Science and Biotechnology,
Shanghai
Jiao Tong University, DongChuang Road 800, 200240 ShangHai, China
The metabolism of drugs in human beings involves a series of enzymes to participate.
The cytochrome
P450s (CYPs) are considered to have closest relationships with drug metabolism. Among CYPs,
CYP2E1 is responsible for four percent drug metabolism and handles carcinogenic molecules,
such as, narcotic, ethanol, acetaminophen, and nitrosamine. In our investigations, we take the
recently released X-ray structure of CYP2E1 from PDB to initiate the molecular docking
operations and dock 12 substrates to the binding site of CYP2E1 using our in-house software
Shanghai Molecular Modeling (SAMM) with the binding pockets were explicitly defined. After
hydrophilic or hydrophobic surface analysis, six molecules (methoxyflurane, acetaminophen,
aniline, benzene, chlorzoxazone, ethanol, N,N-dimethyl formamide and theophylline) were
selected to perform 4ns molecular dynamics simulations. It was found that Thr 303 plays a central
role in interacting with substrates. And some residues (Leu368, Ile115, Phe298, and Val364) can
stabilize substrates by forming corresponding hydrogen bonds. In addition, Ile115, Phe116,
Asp295, Phe298, Thr 303 and Leu368 were found to have close relationships with the binding
pocket CYP2E1 with substrates. All these findings are useful for conducting mutagenesis studies,
providing insights into personalziation of drug treatments and stimulating novel strategies for
finding desired personalized drugs.
2. [1] Jin-Young Park and Dan Harris, J. Med. Chem. 2003, 46, 1645.
Conventional and microwave synthesis of -(substituted
heir biological
1
N-3-{(2-substituted aryl-5
aryledene)-4-oxo- thiazolidene)-cabamyl}-propy - 6-nitroindazole derivatives and t
significance

Pushkal Samadhiya and S.K. Srivastava*
Synthesis organic laboratory, Department of
Chemistry,
Dr. H.S. Gour University (A Central University), Sagar- 470003
India
Email: pushkal83@rediffmail.com
3. Heterocycle is important and wide class of chemistry which contain at least one heteroatom in ring.
Indazole is also heterocyclic compound because contain two nitrogen atoms in five membered ring.
Indazoles are a type of diazoles which shows interesting biological properties such as anti-HIV,
antiemetic, antitumor, antidepressant, anti-inflammatory, analgesic, antipyretic, dopamine
antagonist and inhibit neuronal nitrogen oxide synthesis. The compounds containing thiazolidene
ring shows various biological activities viz. antibacterial, antifungal, anticancer etc. indazole
reflects the reactivity of both pyridine and pyrrol. We are inspired with this dual behavior of
indazole and reported the synthesis of 1
N-3-{(2-substituted aryl-5-(substituted aryledene)-4-oxothiazolidene)-cabamyl}-propyl-6-nitroindazole
(V) by conventional and microwave methods.
These compounds have been synthesized in five different steps, firstly alkylation took place at 1N
position of 6-nitroindazole by Br(CH ) Cl to yield 1N-(3-chloro-propyl)-6-nitroindazole,
2 3
compound (I). The compound(I) on reaction with urea at room temperature gave
1N-{3-(carbamyl) -propyl}-6-nitroindazole,compound(II) which on reaction with several
substituted aromatic carbonyls afforded
1N-{3-(substituted-arylidine-carbamyl)-propyl]-6-nitroindazoles, compound(III). The
comound(III) on fur-ther reaction with HSCH COOH in the presence of anhydrous ZnCl
2 2
furnished the final products compound(IV). The compound(IV) undergoes knovenalgel
condensation reac-tion on treatment with several aromatic carbonyls in the presence of EtONa
yielded compound(V). Microwave assisted synthesis of compounds(I-V) gave better yield in the
comparison to conventional method and prevent impurities and wastage of organic solvents. The
compounds(I-V) synthesized by both methods were characterized by IR,
Stu th
m
1
HNMR, 13
CNMR,
FAB-Mass and chemical methods. All synthesized products(I-IV) were evaluated for their
antimicrobial activity against some selected microorganisms, which showed acceptable activity.
dying on the mechanism of action of biocidal Guanides polymers to the bacteria wi
olecular
dynamics
method
Yukun Wang Ruoxu Gu Dong-Qing Wei*
Department of Bioinformatics and Biostatistics, College of Life Sciences
and Biotechnology, Shanghai
Jiao Tong University, Shanghai, P. R. China, 200240
* Correspondence: dqwei@sjtu.edu.cn
Knowledge of the mechanism of action of
biocidal guanides polymers is crucial for the development of
new compounds to combat microbial pathogens. However it is very difficult to study the interaction
between Antimicrobial agent and microorganism directly because of the existence of cytoplasmic
membrane. To this end, computational studies on the interaction of known membrane-active
antimicrobial polymers with phospholipids bilayers reveal spontaneous membrane insertion and
cooperative action at low and high concentrations, respectively. We constructed a piece of mammalian
membrane with pure POPC and a piece of prokaryotic membrane with POPE:POPG=3:7. Under 30 ns’
MD equilibrium, they had reached the thermodynamics stable state. Then we added the biocidal
guanides polymer molecules to the two equilibrated membranes and went on to run for 20ns. It was

discovered that the antimicrobial agents was adsorbed closely to the membrane after the 20ns’
simulation and frequently changed their structure to search for the conformation appropriate to insert
the membrane.
Key words: Biocidal guanides Polymers、molecular dynamics、cytoplasmic membrane.
PO-034
Ab initio molecular
dynamics study of solid β-HMX
Jing Chang1,2, Dong-Qing Wei1*, Xiang-Rong Chen2,3
1. College of Life Science and Biotechnology, Shanghai Jiao
tong University, Shanghai
200240, China
2. School of Physical
Science and Technology, Sichuan University, Chengdu 610064, China;
3. International Centre for Materials Physics, Chinese Academy of Sciences, Shenyang 110016, China;
The dynamical behavior of β-octahydro-1,3,5,7-tetranitro-1,3,5,7- tetrazocine (β-HMX)
crystal has been studied using the Car-Parrinello ab initio molecular dynamics scheme, the
optimized geometry of the molecule in the unit cell are shown to be in good agreement
with the available experimental data[1] and other theoretical results[2,3]. The temperature
effect on the bulk structure and properties has been investigated. Following the dynamics
for a time scale of up to 50 ps and temperatures at about 3800K allows the construction of
effective rate laws for typical products such as H2O, N2, CO2, and CO. In addition, the
vibrational frequencies of a molecular system from molecular dynamics simulations is
presented based on a localization criterion for the Fourier transformed velocity
time-correlation functions of the effective modes. The temperature-induced frequency
shifts of these modes are calculated and discussed in detail.
Keywords: β-HMX, first-principles molecular dynamics, CPMD,
vibrational frequencies
[1] Choi C S. and Boutin H.P. Acta Crystallogr. B 1970, 26, 1235.
[2] Lu L Y, Wei D Q, Chen X R, Lian, D, Ji, G F, Zhang, Q M and Gong, Z Z. Molecular
Physics, 2008, 106, 2569.
[3] Brand H V, Rabie R L,Funk
D J, Diaz-Acosta I, Pulay P, Lippert T K. J. Phys. Chem. B,
2002, 106, 10594.
PO-035
Molecular Dynamics Studies on phospholamban in membranes
Peng
Lian, Jingfang Wang, Dongqing Wei*
Department of Bioinformatics and Biostatistics,
College of Life Sciences and Biotechnology, Shanghai
Jiao Tong University, Shanghai, P. R. China, 200240
* Correspondence: dqwei@sjtu.edu.cn
Phospholamban (PLN) is a membrane protein
with 52 residues which regulating the
activity of sarcoplasmic reticulum Ca2+-ATPase. Different stable conformations,
bellflower model and pinwheel model, were found on the surface of muscle cells. In order
to explore the reasons it exhibits different conformation and the mechanism it realize its
biological function, we have carried out molecular dynamics simulations on
unphosphorylated and phosphorylated of both models in POPC membrane. It is found that
the phosphate group plays an important role in regulating the activity of PLN through
changing the flexibility of monomer helix. The different conformations of phosphorylated
monomer helix become similar after long time simulation. This suggests that different

conformations may convert to each other via phosphorylation and dephosphrylation.
[1] Nathaniel J. Traaseth, Lei Shi, Raffaello Verardi et al. PNAS 2009 106 10165
[2] Becucci L, Cembran A, Karim CB et al. Biophys J. 2009 96 L60
[3] Kim T, Lee J. Im W Proteins 2009 76 86
PO-036
Support vector machines for identification of DNA-binding residues in proteins using
a hybrid feature
Yi Xiong1,2, Juan Liu1
and Dong-Qing Wei2
1School of Computer, Wuhan University, Wuhan
430079
2 College of Life Science and Biotechnology, Shanghai Jiaotong
University, Shanghai
200240
Protein–DNA
interactions are crucial for a variety of essential biological activities. An automatic and
reliable identification of DNA-binding residues in DNA-binding proteins is important for site-directed
mutagenesis and functional annotation. Toward this end, a pattern recognition method can be
developed using the distinguished features derived from the increasing number of determined
structures of protein–DNA complexes in Protein Data Bank. Here, we developed a series of classifiers
using support vector machines to identify DNA-binding residues in proteins with different
combinations of various features, which are comprised of evolutionary information of the amino acid
sequence, residue solvent accessibility, electrostatic potential and secondary structure. In addition, we
designed a heuristic undersampling scheme for preprocessing the training datasets and a novel
encoding strategy for the solvent accessibility feature. Our results indicate that the best classification
performance was obtained by a SVM classifier that utilizes a combination of evolutionary information,
residue solvent accessibility and second structure information. Finally, we applied our method in a
dataset of 62 protein–DNA complexes in comparison with other published studies. The observation
suggests that our method achieved a higher performance with an overall accuracy 84.5% on a 10-fold
cross validation test.
Keywords: Protein–DNA
Interaction; DNA-binding Residue; Support Vector Machine
PO-037
Inferring gene regulatory networks from ChIP-chip, TF knock-out and expression data
Lihua Jiang and Qi Liu
Department of Bioinformatics
and Biostatistics, College of Life Sciences and Biotechnology, Shanghai
Jiao Tong University, Shanghai, P. R. China, 200240
Uncovering the underlying regulatory mechanism remains
a challenge in bioinformatics
studies. With the availability of various kinds of high-throughput biological data,
researchers are trying to reconstruct the gene regulatory networks on a genomic scale.
Since each single data source provides only partial and complementary information of the
regulatory relationships, combining diverse data sources is expected to get more reliable
networks.
Here we present
a method to infer the regulatory networks by combining ChIP-chip, TF (transcription
factor) knock-out and expression data. Our method is the first approach to combine these three kinds of
data. ChIP-chip and TF knock-out data provide direct and complementary evidence on transcriptional
regulation. We use these two kinds of data to find the core regulatory module and then we refine the
module by the indirect evidence inferred from the expression data. The results are validated by the
YEASTRACT, high quality ChIP-chip datasets, literatures and Gene Ontology enrichment analysis.

The results demonstrate that our method achieves good performances on predicting transcriptional
regulations.
Keywords: regulatory networks, ChIP-chip, TF knock-out and expression data
PO-038
The development
of SNP prediction algorithm for CYtochrome P450
Li Li and Dongqing Wei
Department of Bioinformatics
and Biostatistics, College of Life Sciences and Biotechnology, Shanghai
Jiaotong University, 800 Dongchuan Road, Minhang District Shanghai, 200240, China
Cytochrome P450 (also called CYPs, P450s and CYP450s), a member of hemoproteins
superfamily[1-3], has been identified from variety of species. The P450s are the most important
enzymes responsible for drug metabolism. They participate in many kinds of catalyze reactions refer to
both exogenous and endogenous compounds. Single nucleotide polymorphisms (SNPs) are the most
frequently occurring genetic variation in the human CYPs, considered as a decisive factor for the
disease susceptibility and drug response. Consequently, SNPs have become one of the most significant
research areas in current human genomic studies.
In the post-genome era, the rapid accumulation of SNP data provides an opportunity to find out SNPs
using computational methods. However, the majority of current predict methods are unsatisfactory due
to the lower prediction accuracy (just about 40%-50%).
In order to solve this problem, we build a support vector machine (SVM) model based on the protein
coded by the gene around CYP450 SNP site and the physical and chemical properties of the
amino acids. By using a wide range of data, we demonstrate the accuracy of this method achieves
65%, which is about 15% higher Compared with the existing machine learning method (including
the random forest method and K-neighbor method) and pattern discovery algorithm. However, the
accuracy of this algorithm is still quite low. Currently, we are making efforts to integrate more
information for further optimization.
References
1.Jing-Fang Wang
and Dong-Qing, Wei*, “Role of Structural Bioinformatics and TCM databases in
Pharmacogenomics”, Pharmacogenomics, 10, Issue 10 (2009).
2.Jing-Fang Wang, Cheng-Cheng Zhang, , Jing-Yi Yan, Kuo-Chen Chou, Dong-Qing Wei* ,
“Structure of cytochrome P450s and personalized drug”, Current Medicinal Chem, 16, 232-244(2009).
3. Jing-Fang Wang , Dong-Qing Wei*, Kuo-Chen Chou, “Pharmacogenomics and Personalized Use of
Drugs”, Current Topics in Medicinal Chemistry, 8, 1573-1579(2008).
Conventional and solvent free syntheses of 1N-3-{(4-substituted
aryl-3-chloro-2-oxo-azetidine)-imido}-propyl-1,2,3 -benzotriazole derivatives: Antimicrobial
activity
Ritu Sharma
and S.D. Srivastava*
Synthesis organic laboratory, Department
of Chemistry,
Dr. H.S. Gour University(A Central University), Sagar- 470003,
India
Email: ritusharmaic@rediffmail.com
Heterocycles bearing nitrogen moieties constitute the core structure of numbers of pharmacologically
and biologically active interesting compounds. The efficiency of azoles as chemotherapeutic agent is
well established. Various derivatives of 1,2,3-benzo-triazole and 2-oxoazetidines exhibit interesting
pharmacological properties including antimicrobial, antifungal, anticancer, analgesic anticonvulsant,
antiinflamma-tory, and CNS depressant. In this work, we focus interest on incorporating azetidinone

and imidopropyl with 1,2,3-benzotriazole in one framework and hope to obtain few compo-unds
having better biological activities. Here we report the synthesis of series of 1N-3-{(4-substituted
aryl-3-chloro-2-oxo-azetidine)-imido}- propyl-1,2,3-benzotriazoles (4) by conventional and microwave
irradiation. Microwave irradiation accelerated synthesis is eco-friendly, reduces reaction time, improve
yield and prevents impurities, and wastage of organic solvents. The titled compounds were synthesized
in four different steps. 1,2,3-benzotriazole on reaction with Cl(CH 2 ) 3 Br at room temperature gave
1N-(3-chloro- propyl)-1,2,3-benzotriazole, compound 1. The compound 1 yielded the condensation
product with urea at room temperature, N-(3-carbamylpropyl)-1,2,3- benzotriazole, compound 2. The
compound 2 on further reaction with several substituted aromatic carbonyls produced
N-{3-(substituted-arylidine carbamyl)-propyl-1,2,3-benzotriazole, compound 3. The compound 3 on
treatment with ClCH
2
oroplast metabolic structure enable stable photosynthetic rates under
COCl in the presence of Et N furnished final products compound 4. The
3
structures of all the newly synthesized com-pounds were confirmed by IR. 1
HNMR, 13
CNMR
FAB-Mass and elemental analysis. It has been observed that in the conventional method, the yield of
all products is slightly lower as compared to microwave induced synthesis. All synthesized
products(1-4) were evaluated for their antimicrobial activity against some selected microorganisms
which showed better results.
Evolutionary changes of chl
environments which can cause high rates of mutation
Zhuo Wang 1,2
, Qi Chen 1
, Xin-guang Zhu 3
, Dongqing Wei 1
, Yixue Li 2
, Lei Liu 2
1.College of life science and technology, Shanghai Jiao Tong University.
2.Shanghai Center for Bioinformation Technology.
3.Department of Plant Biology, University of Illinois at Urbana-Champaign
Chloroplast evolved from cyanobacteria as a result of endosymbiosis. Our previous study has
suggested that chloroplast metabolic network, compared to its ancestor cyanobacteria, became denser
around the Calvin cycle though the overall metabolic network became looser. We hypothesize that such
changes in chloroplast metabolic structure enable chloroplast capacity of keeping relative stable
photosynthetic rate under mutational pressure. We use Flux Balance Analysis (FBA) to test this
hypothesis by comparing metabolic networks of chloroplast and one representative cyanobacteria
Synechococcus sp. WH8102 (syw).
The metabolic networks of chloroplast
and syw were reconstructed based on Database of
Chloroplast/Photosynthesis Related Genes and KEGG database respectively. We use FBA to simulate
the flux distribution in the two networks, and evaluate the flux variation under different in silico
single-enzyme knockouts. The target function is maximization of the rate of phosphoglycerate (PGA)
formation, which is the key step of CO2 fixation. Constraints of fluxes in different reactions were
extracted by literature survey.
Our FBA analysis suggested a) Chloroplast
has higher fluxes in Calvin cycle including the rate of PGA
formation, compared to syw; b) Fluxes in Calvin cycle of chloroplast show higher resistances to null
mutation compared to syw; c) Fluxes through reactions in Calvin cycle show higher resistance to null
mutation than those outside Calvin cycle in both chloroplast and syw.
In conclusion, the FBA on metabolic networks of chloroplast and cyanobacteria
suggested that the
changes of metabolic structure enable chloroplast keep more robust and stable photosynthesis under
environment where higher rate of mutation is possible, e.g. when UV light is abundant.
[1] Z Wang, XG Zhu, YZ Chen, YY Li, J Hou, YX Li, L Liu. Exploring photosynthesis evolution by
comparative analysis of metabolic networks between chloroplasts and photosynthetic bacteria. BMC

Genomics, 2006, 7:100.
[2] KJ Kauffman, P Prakash, JS Edwards. Advances in flux balance analysis. Current Opinion in
Biotechnology, 2003, 14:491–496.
PO-041
Class I Phospho-inositide-3-kinases
(PI3Ks) Isoform-specific Inhibition Study by the
Combination of Docking and Molecular Dynamics Simulation
Han, Ming
PO-042
Molecular Dynamics Simulation studies on structural changes and catalytic mechanism of T1
lipase at different temperatures
-Qing Wei 3
Ying Wang ,*
1
, Jing-Fang Wang 2
,*,Dong
1
Department of Bioinformatics and Biostatistics, College of Life Science and Biotechnology, Shanghai
Jiaotong University, Shanghai 200240, China
2
Bioinformatics Center, Key Laboratory of Systems
Biology, Shanghai Institutes for Biological
Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Molecular Dynamics (MD) simulations of T1 lipase movements have revealed the structural
aspects of the T1 lipase responsible for varying activity at different temperature and domain
movements responsible for activity. An interesting structure of T1 lipase was found by using the
long time‐scale molecular dynamics simulations. Overall, the whole T1 lipase molecular was cut
into eight regions in charge of divers functions by the centralβ‐sheet consisting of seven strands
which showed higher stability and constructed the main structure. The active site was
surrounded or covered by the regions which liked petals opening or closing during
temperature‐induced simulations. The active site was on the region 3which was relatively stable.
However, region 2 was accompanied by a large flexibility and dynamics under varying
temperature conditions, so this region was temperature receptor of the T1 lipase. Our studies
explained that T1 lipase had high catalytic activity at 70℃, because exposure time of the active
site was long and the size of the pocket was comfortable. In addition, at lower or higher
temperature, the structure of T1 lipase played great changes and the surface area exposed to
solvent was too large, thus the activity was lost. All these findings might provide significant
evidence for the catalytic mechanism of T1 lipase.