10 A niversary of IIMCB

Current Research
The Laboratory of Bioinformatics and Protein Engineering
is involved in theoretical and experimental research on
the sequence-structure-function relationships in proteins
and nucleic acids and in macromolecular complexes. The
laboratory is comprised of three sections:
• A section devoted to the development of computer
software for analysis of biological macromolecules.
The bioinformatics tools include a suite of programs for
protein structure prediction and analysis available via the
website https://iimcb.genesilico.pl/toolkit/ (MetaServer
for primary, secondary, and tertiary structure prediction,
methods for template-based and de novo modeling of
three-dimensional protein structures, MetaMQAP for
quality assessment of protein models, FILTREST3D for
discrimination of models according to their agreement
with experimental data, and COLORADO3D for mapping
the sequence of features onto the protein structure); a
standalone program PROTMAP2D for analysis of contact
and distance maps in protein structures (http://iimcb.
genesilico.pl/protmap2d.htm); the MODOMICS database
for systems biology of RNA modification (http://iimcb
genesilico.pl/modomics/) and the REPAIRTOIRE database
for systems biology of DNA repair (http://iimcb.genesilico.
pl/repairtoire/).
Fig. Distribution of Type II restriction enzyme sequences among known superfamilies/folds (published in Nucleic Acids Res 2008 Jun;36(11):3552-69).
a) Representative structures of nucleases with catalytic domains of different folds: PD-(D/E)XK – restriction enzyme BamHI (PDB: 3bam), HNH – T4
endonuclease VII (PDB: 1en7), GIY-YIG – restriction enzyme BfiI (PDB: 2c1l), PLD – homing endonuclease I-TevI (PDB: 1mk0), HALFPIPE – restriction
enzyme PabI (PDB: 2dvy)
b) Results of clustering of nuclease domains of Type II REases from REBASE and their homologues in the nr and env_nr database with CLANS. Sequences
and structures are colored according to the their assignment to superfamilies: green – PD-D(E)XK, blue – HNH, yellow – GIY-YIG, violet – PLD, light
blue – HALFPIPE, red – unclassified. Connections between dots represent the degree of pairwise sequence similarity, as quantified by BLAST P-value
(the darker the line, the higher similarity). The original figure is accessible from (Nucleic Acid Research (http://nar.oxfordjournals.org/cgi/content/
full/36/11/3552) (author: Jerzy Orłowski).
30 Annual Report 2008
• A section devoted to the application of bioinformatics
software to make biologically and biomedically relevant
predictions. Recently published research includes
phylogenomic analyses of various nuclease and
methyltransferase superfamilies, and detailed structure
prediction and modeling of individual proteins that are of
wide interest (e.g. EXOG, a mitochondrial 5’–3’ exonuclease
potentially involved in apoptosis). Theoretical research of
this section frequently involves collaboration with other
laboratories interested in obtaining a structural model
for their favorite proteins and experimental testing of our
predictions. Recent modeling analyses (published in 2008)
include various restriction and homing endonucleases
and RNA modification enzymes.
• A section devoted to experimental research on proteins
and nucleic acids using methods of biochemistry,
molecular biology, and cell biology. There are three
principal types of analyses carried out by researchers from
our “wet lab”:
1. Experimental testing of functional predictions by gene
cloning, protein expression, purification, development of
in vitro and in vivo functional assays and biochemical and
cellular characterization.
2. Experimental testing of structural predictions by
application of low-resolution structural probing
methods, such as mutagenesis, chemical modification,