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PROTOCOL
Computational proteinligand docking and virtual drug screening with the AutoDock suite
Stefano Forli, Ruth Huey, Michael E Pique, Michel F Sanner, David S Goodsell & Arthur J Olson
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA. Correspondence should be addressed to A.J.O. ([email protected]).
Published online 14 April 2016; http://dx.doi.org/10.1038/nprot.2016.051
Web End =doi:10.1038/nprot.2016.051
Computational docking can be used to predict bound conformations and free energies of binding for small-molecule ligands to macromolecular targets. Docking is widely used for the study of biomolecular interactions and mechanisms, and it is applied to structure-based drug design. The methods are fast enough to allow virtual screening of ligand libraries containing tens of thousands of compounds. This protocol covers the docking and virtual screening methods provided by the AutoDock suite of programs, including a basic docking of a drug molecule with an anticancer target, a virtual screen of this target with a small ligand library, docking with selective receptor flexibility, active site prediction and docking with explicit hydration. The entire protocol will require ~5 h.
2016Macmillan Publihers Limited. All rights reserved.
INTRODUCTION
Computational docking is widely used for the study of protein ligand interactions and for drug discovery and development. Typically, the process starts with a target of known structure, such as a crystallographic structure of an enzyme of medicinal interest. Docking is then used to predict the bound conformation and binding free energy of small molecules to the target. Single docking experiments are useful for exploring the function of the target, and virtual screening, in which a large library of compounds are docked and ranked, may be used to identify new inhibitors for drug development.
AutoDock is a suite of free open-source software for the computational docking and virtual screening of small molecules to macromolecular receptors. The suite currently includes several complementary tools:
AutoDock Vina: a turnkey computational docking program that is based on a simple scoring function and rapid gradient-optimization conformational search1.
AutoDock: a computational docking program based on an empirical free-energy force eld and rapid Lamarckian genetic algorithm search method2,3.
Raccoon2: an interactive graphical tool for virtual screening and analysis4.
AutoDockTools (ADT): an interactive graphical user interface (GUI) for coordinate preparation, docking and analysis5.
AutoLigand: a program for predicting optimal...