MIOSS Rui MV Abreu

MOLA: an open source tool for virtual screening with
AutoDock4/Vina using a multi-platform set of
computers … and ChemT
Molecular Informatics Open Source Software Workshop
4-6 May, 2011
Escola Superior Agrária de Bragança-IPB
Rui Abreu
Escola de Ciências
Centro de Química
Universidade do Minho

MOLA
-a GUI tool that automates parallel virtual screening,
using AutoDock4 and/or Vina as protein-ligand docking
algorithm in bootable non-dedicated computer clusters.

ChemT
-library generator of chemical analogs, based on a
chemical template of interest.

Protein-Ligand Docking
-Tries to predict the binding of a small molecule
(ligand) to a protein structure.
-Structure-Based Drug Design (SBDD) method.
-Protein-ligand Docking can be use to perform
VIRTUAL SCREENING of a large dataset
(library) of potential ligands, in search of lead
compounds.
-Protein-ligand Docking predicts a POSE of the
ligand (binding mode) and a SCORE of binding
affinity representing the binding strength.

AutoDock4 and AutoDock Vina
-Developed at the Molecular Graphics Lab, Scripps
Research Institute.
-AutoDock4 is free and is available under the
GNU/GPL. AutoDock Vina is available under the Apache
license, allowing commercial and non-commercial use
and redistribution.
-Scoring functions used by AutoDock4 and AutoDock
Vina are different, either program may provide a
better result when using a given protein target.

MOLA
-MOLA automates ligand preparation, parallel
AutoDock4/Vina jobs distribution and result analysis.
-A open-office spreadsheet file opens with the ligands
ranked by binding energy and distance to the active
site.
-MOLA is integrated in a remastered Linux LiveCD
based on Pelican HPC. Shell script and Xdialog.
-MOLA is ideal virtual screening in a limited number of
multi-platform heterogeneous computers available and
no access to dedicated Linux computer clusters.
www.esa.ipb.pt/~ruiabreu/mola
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MOLA

ChemT
-ChemT automatically generates 3D chemical compounds
libraries, based on a user-defined chemical template, in an
easy-to-use approach.
-Several options are available including: LRF filters, individual
properties filters and multiple files option when saving
compounds files. Also, ChemT supports file formats more
frequently used in Virtual Screening.
-ChemT can be a useful tool in the drug discovery process, by
automatically generating compound libraries, which can be
virtually evaluated using different Virtual Screening tools.
-Csharp and OpenBabel OBDotNet library.
www.esa.ipb.pt/~ruiabreu/chemt
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Example of MOLA and ChemT usage
Virtual Screening of thieno[3,2-b]pyridines as potential
inibitors against VEGFR-2 (Vascular Endothelial
Growth Factor Receptor-2) protein target
● -VEGFR-2 is a tyrosine kinase membrane receptor involved in
angiogenesis signaling pathways.
●
-Several VEGFR-2 inhibitors have emerged as promising antiangiogenic
agents for possible treatment against a wide variety
of cancers including: sorafenib (Bay 43-9006), sunitinib (SU-
11248), and pazopanib (GW786034). Approved for the
treatment of advanced renal cell carcinoma.
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VEGFR-2
-Use MOLA for virtual screening of thieno[3,2-b]pyridines derivatives.
-Use ChemT to perform successive rounds of thieno[3,2-b]pyridines
library generation in an attempt to find new VEGFR-2 inhibitor leads.
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VEGFR-2
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Acknowledgements
Hugo Froufe
Prof. Isabel Ferreira
CIMO-ESA/IPB, Bragança Polithecnic Institute, Portugal
Prof. Maria-João Queiroz
Chemical Center, Minho University, Portugal
Thanks to Open Source: OpenBabel, Indigo
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