Summary
AutoDock 2.4 predicts the bound conformations of a small, flexible ligand to a nonflexible macromolecular target of known structure. The technique combines simulated annealing for conformation searching with a rapid grid-based method of energy evaluation based on the AMBER force field. AutoDock has been optimized in performance without sacrificing accuracy; it incorporates many enhancements and additions, including an intuitive interface. We have developed a set of tools for launching and analyzing many independent docking jobs in parallel on a heterogeneous network of UNIX-based workstations. This paper describes the current release, and the results of a suite of diverse test systems. We also present the results of a systematic investigation into the effects of varying simulated-annealing parameters on molecular docking. We show that even for ligands with a large number of degrees of freedom, root-mean-square deviations of less than 1 Å from the crystallographic conformation are obtained for the lowest-energy dockings, although fewer dockings find the crystallographic conformation when there are more degrees of freedom.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
BlaneyJ.M. and DixonJ.S., Perspect. Drug Discov. Design, 1 (1993) 301.
KuntzI.D., MengE.C. and ShoichetB.K., Acc. Chem. Res., 27 (1994) 117.
RosenfeldR., VajdaS. and DeLisiC., Annu. Rev. Biophys. Biomol. Struct., 24 (1995) 677.
BöhmH.-J., J. Comput.-Aided Mol. Design, 6 (1992) 593.
KuntzI.D., BlaneyJ.M., OatleyS.J., LangridgeR. and FerrinT.E., J. Mol. Biol., 161 (1982) 269.
GoodsellD.S. and OlsonA.J., Proteins Struct. Funct. Genet., 8 (1990) 195.
GoodsellD.S., LaubleH., StoutC.D. and OlsonA.J., Proteins Struct. Funct. Genet., 17 (1993) 1.
LunneyE.A., HagenS.E., DomagalaJ.M., HumbletC., KosinskiJ., TaitB.D., WarmusJ.S., WilsonM., FergusonD., HupeD., TumminoP.J., BaldwinE.T., BhatT.N., LiuB., and EricksonJ.W., J. Med. Chem. 37 (1994) 2664.
Vara PrasadJ.V.N., ParaK.S., OrtwineD.F., DunbarJr.J.B., FergusonD., TumminoP.J., HupeD., TaitB.D., DomagalaJ.M., HunbletC., BhatT.N., LiuB., GuerinD.M.A., BaldwinE.T., EricksonJ.W. and SawyerT.K., J. Am. Chem. Soc., 116 (1994) 6989.
StoddardB.L. and KoshlandD.E., Nature, 358 (1992) 774.
Hart, W.E., Ph.D. Thesis, University of California, San Diego, CA, at ‘ftp://ftp.cs.sandia.gov/pub/papers/wehart/thesis.ps.gz’.
MaillotP.-G., In GlassnerA.S. (Ed.) Graphics Gems, Academic Press, New York, NY, 1990, pp. 498–515.
WattA. and WattM., Advanced Animation and Rendering Techniques — Theory and Practice, ACM Press, New York, NY, and Addison-Wesley Publishing Company, Wokingham, U.K., 1992.
PattabiramanN., LevittM., FerrinT.E. and LangridgeR., J. Comput. Chem., 6 (1985) 432.
GoodfordP.J., J. Med. Chem., 28 (1985) 849.
WeinerS.J., KollmanP.A., CaseD.A., SinghU.C., GhioC., AlagonaG., ProfetaJr.S. and WeinerP., J. Am. Chem. Soc., 106 (1984) 765.
Van derWaalsJ.H., Lehrbuch der Thermodynamik, Part 1, Mass and Van Suchtelen, Leipzig, Germany, 1908.
BashfordD. and GerwertK., J. Mol. Biol., 224 (1992) 473.
BashfordD. and KarplusM., Biochemistry, 29 (1990) 10219.
GilsonM.K. and HonigB., Nature, 330 (1987) 84.
HonigB. and NichollsA., Science, 268 (1995) 1144.
MehlerE.L. and SolmajerT., Protein Eng., 4 (1991) 903.
MarquartM., WalterJ., DeisenhoferJ., BodeW. and HuberR., Acta Crystallogr., Sect. B, 39 (1983) 480.
PoulosT.L., FinzelB.C. and HowardA.J., J. Mol. Biol., 195 (1987) 687.
PadlanE.A., CohenG.H. and DaviesD.R., Ann. Immunol. (Paris), Sect. C, 136 (1985) 271.
WeberP.C., OhlendorfD.H., WendolskiJ.J. and SalemmeF.R., Science, 243 (1989) 85.
LamP.Y.S., JadhavP.K., EyermanC.J., HodgeC.N., RuY., BachelerL.T., MeekJ.L., OttoM.J., RaynerM.M., WongY., ChangC.-H., WeberP.C., JacksonD.A., SharpeT.R. and Erickson-ViitanenS., Science, 263 (1994) 380.
WeisW.I., BruengerA.T., SkehelJ.J. and WileyD.C., J. Mol. Biol., 212 (1990) 737.
McDonaldI.K. and ThorntonJ.M., J. Mol. Biol., 239 (1994) 777.
LeachA.R., ProutC.K. and DolataD.P., J. Comput.-Aided Mol. Design, 4 (1990) 271.
FriedmanA.R., RobertsV.A. and TainerJ.A., Proteins Struct. Funct. Genet., 20 (1994) 15.
Author information
Authors and Affiliations
Additional information
The AutoDock 2.4 suite is written in ANSI C, and is supplied with Makefiles for the following platforms: Convex, DEC Alpha OSF/1, Hewlett-Packard Precision Architecture, Silicon Graphics, and Sun. The AutoDock suite of programs is freely available to the noncommercial scientific community and to educational establishments. Further information, including additional figures and MPEG animations showing all docked conformations for each test system, can be found at the following URL: http://www.scripps.edu/pub/olson-web/doc/autodock.
Rights and permissions
About this article
Cite this article
Morris, G.M., Goodsell, D.S., Huey, R. et al. Distributed automated docking of flexible ligands to proteins: Parallel applications of AutoDock 2.4. J Computer-Aided Mol Des 10, 293–304 (1996). https://doi.org/10.1007/BF00124499
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00124499