Ligand docking and binding site analysis with PyMOL and Autodock/Vina

Docking of small molecule compounds into the binding site of a receptor and estimating the binding affinity of the complex is an important part of the structure-based drug design process. For a thorough understanding of the structural principles that determine the strength of a protein/ligand complex both, an accurate and fast docking protocol and the ability to visualize binding geometries and interactions are mandatory. Here we present an interface between the popular molecular graphics system PyMOL and the molecular docking suites Autodock and Vina and demonstrate how the combination of docking and visualization can aid structure-based drug design efforts.

[1]  Arthur J. Olson,et al.  AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading , 2009, J. Comput. Chem..

[2]  H Edelsbrunner,et al.  Analytical shape computation of macromolecules: II. Inaccessible cavities in proteins , 1998, Proteins.

[3]  David S. Goodsell,et al.  Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function , 1998 .

[4]  Gerard Pujadas,et al.  BDT: an easy-to-use front-end application for automation of massive docking tasks and complex docking strategies with AutoDock , 2006, Bioinform..

[5]  M F Sanner,et al.  Python: a programming language for software integration and development. , 1999, Journal of molecular graphics & modelling.

[6]  Michal Otyepka,et al.  Identification of tunnels in proteins, nucleic acids, inorganic materials and molecular ensembles , 2007, Biotechnology journal.

[7]  J. Bajorath,et al.  Docking and scoring in virtual screening for drug discovery: methods and applications , 2004, Nature Reviews Drug Discovery.

[8]  David S. Goodsell,et al.  Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function , 1998, J. Comput. Chem..

[9]  H. Edelsbrunner,et al.  Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand design , 1998, Protein science : a publication of the Protein Society.

[10]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[11]  Jaques Reifman,et al.  DOVIS: an implementation for high-throughput virtual screening using AutoDock , 2008, BMC Bioinformatics.

[12]  S Subramaniam,et al.  Analytical shape computation of macromolecules: I. molecular area and volume through alpha shape , 1998, Proteins.

[13]  Jaroslav Koca,et al.  CAVER: a new tool to explore routes from protein clefts, pockets and cavities , 2006, BMC Bioinformatics.

[14]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[15]  David S. Goodsell,et al.  A semiempirical free energy force field with charge‐based desolvation , 2007, J. Comput. Chem..

[16]  Nathan A. Baker,et al.  Electrostatics of nanosystems: Application to microtubules and the ribosome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Kristian Rother,et al.  eMovie: a storyboard-based tool for making molecular movies. , 2007, Trends in biochemical sciences.