Using AutoDock for Ligand‐Receptor Docking

Garrett M. Morris1, Ruth Huey1, Arthur J. Olson1

1 The Scripps Research Institute, La Jolla, California
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 8.14
DOI:  10.1002/0471250953.bi0814s24
Online Posting Date:  December, 2008
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


This unit describes how to set up and analyze ligand‐protein docking calculations using AutoDock and the graphical user interface, AutoDockTools (ADT). The AutoDock scoring function is a subset of the AMBER force field that treats molecules using the United Atom model. The unit uses an X‐ray crystal structure of Indinavir bound to HIV‐1 protease taken from the Protein Data Bank (UNIT 1.9) and shows how to prepare the ligand and receptor for AutoGrid, which computes grid maps needed by AutoDock. Indinavir is prepared for AutoDock, adding the polar hydrogens, and partial charges, and defining the rotatable bonds that will be explored during the docking. The input files for AutoGrid and AutoDock are created, and then the grid map calculation run, followed by the docking calculation in AutoDock. Finally, this unit describes some of the ways the results can be analyzed using AutoDockTools. Curr. Protoc. Bioinform. 24:8.14.1‐8.14.40. © 2008 by John Wiley & Sons, Inc.

Keywords: AutoDock; protein‐ligand docking; virtual screening; computer‐aided drug design

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Download and Install AutoDock, AutoGrid, and AutoDockTools
  • Basic Protocol 2: Preparing the Macromolecule
  • Basic Protocol 3: Preparing the Ligand
  • Basic Protocol 4: Saving the Macromolecule in PDBQT Format
  • Basic Protocol 5: Preparing the Flexible Residues (Optional)
  • Basic Protocol 6: Preparing the Grid Parameter File
  • Basic Protocol 7: Starting AutoGrid 4
  • Basic Protocol 8: Setting Up the Docking
  • Basic Protocol 9: Starting AutoDock 4
  • Basic Protocol 10: Reading Docking Logs
  • Basic Protocol 11: Visualizing Docked Conformations
  • Basic Protocol 12: Clustering Conformations
  • Basic Protocol 13: Visualizing Conformations in the Complex
  • Guidelines for Understanding Results
  • Commentary
  • Literature Cited
  • Figures
  • Tables
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
   Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., and Bourne, P.E. 2000. The Protein Data Bank. Nucleic Acids Res. 28:235‐242.
   Chen, Z., Li, Y., Chen, E., Hall, D.L., Darke, P.L., Culberson, C., Shafer, J.A., and Kuo, L.C. 1994. Crystal structure at 1.9‐Å resolution of human immunodeficiency virus (HIV) II protease complexed with L‐735,524, an orally bioavailable inhibitor of the HIV proteases. J. Biol. Chem. 269:26344‐26348.
   Cole, J.C., Murray, C.W., Nissink, J.W., Taylor, R.D. and Taylor, R. 2005. Comparing protein‐ligand docking programs is difficult. Proteins 60:325‐332.
   Cozzini, P., Kellogg, G.E., Spyrakis, F., Abraham, D.J., Costantino, G., Emerson, A., Fanelli, F., Gohlke, H., Kuhn, L.A., Morris, G.M., Orozco, M., Pertinhez, T.A., Rizzi, M., and Sotriffer, C.A. 2008. Target flexibility: An emerging consideration in drug discovery and design. J. Med. Chem. 51:6237‐6255.
   Gasteiger, J. and Marsili, M. 1978. A new model for calculating atomic charges in molecules. Tetrahedron Lett. 34:3181‐3184.
   Goodsell, D.S. and Olson, A.J. 1990. Automated docking of substrates to proteins by simulated annealing. Proteins 8:195‐202.
   Hetenyi, C. and van der Spoel, D. 2002. Efficient docking of peptides to proteins without prior knowledge of the binding site. Protein Science 11:1729‐1737.
   Hetenyi, C. and van der Spoel, D. 2006. Blind docking of drug‐sized compounds to proteins with up to a thousand residues. FEBS Lett. 580:1447‐1450.
   Huey, R., Morris, G.M., Olson, A.J., and Goodsell, D.S. 2007. A semi‐empirical free energy force field with charge‐based desolvation. J. Comput. Chem. 28:1145‐1152.
   Kontoyianni, M., McClellan, L.M. and Sokol, G.S. 2004. Evaluation of docking performance: Comparative data on docking algorithms. J. Med. Chem. 47:558‐565.
   Kontoyianni, M., Madhav, P., Suchanek, E. and Seibel, W. 2008. Theoretical and practical considerations in virtual screening: A beaten field? Curr. Med. Chem. 15:107‐116.
   Leach, A.R., Shoichet, B.K. and Peishoff, C.E. 2006. Prediction of protein‐ligand interactions. Docking and scoring: Successes and gaps. J. Med. Chem. 49:5851‐5855.
   Lin, J.H., Perryman, A.L., Schames, J.R., and McCammon, J.A. 2002. Computational drug design accommodating receptor flexibility: The relaxed complex scheme. J. Am. Chem. Soc. 124:5632‐5633.
   Lin, J.H., Perryman, A.L., Schames, J.R., and McCammon, J.A. 2003. The relaxed complex method: Accommodating receptor flexibility for drug design with an improved scoring scheme. Biopolymers 68:47‐62.
   McCammon, J.A. 2005. Target flexibility in molecular recognition. Biochim. Biophys. Acta 1754:21‐24.
   Morris, G.M., Goodsell, D.S., Huey, R., and Olson, A.J. 1996. Distributed automated docking of flexible ligands to proteins: Parallel applications of AutoDock 2.4. J. Comput. Aided Mol. Des. 10:293‐304.
   Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., and Olson, A.J. 1998. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 19:1639‐1662.
   Sanner, M.F., Olson, A.J., and Spehner, J.C. 1996. Reduced surface: An efficient way to compute molecular surfaces. Biopolymers 38:305‐320.
   Schames, J.R., Henchman, R.H., Siegel, J.S., Sotriffer, C.A., Ni, H., and McCammon, J.A. 2004. Discovery of a novel binding trench in HIV integrase. J. Med. Chem. 47:1879‐1881.
   Shoichet, B.K., McGovern, S.L., Wei, B., and Irwin, J.J. 2002. Lead discovery using molecular docking. Curr. Opin. Chem. Biol. 6:439‐446.
   Sousa, S.F., Fernandes, P.A., and Ramos, M.J. 2006. Protein‐ligand docking: Current status and future challenges. Proteins 65:15‐26.
   Vaque, M., Arola, A., Aliagas, C., and Pujadas, G. 2006. BDT: An easy‐to‐use front‐end application for automation of massive docking tasks and complex docking strategies with AutoDock. Bioinformatics 22:1803‐1804.
   Warren, G.L., Andrews, C.W., Capelli, A.M., Clarke, B., LaLonde, J., Lambert, M.H., Lindvall, M., Nevins, N., Semus, S.F., Senger, S., Tedesco, G., Wall, I.D., Woolven, J.M., Peishoff, C.E., and Head, M.S. 2006. A critical assessment of docking programs and scoring functions. J. Med. Chem. 49:5912‐5931.
PDF or HTML at Wiley Online Library