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DARWIN: A program for docking flexible molecules
Author(s) -
Taylor Jeffrey S.,
Burnett Roger M.
Publication year - 2000
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/1097-0134(20001101)41:2<173::aid-prot30>3.0.co;2-3
Subject(s) - docking (animal) , computation , computer science , darwin (adl) , chemistry , molecule , computational chemistry , algorithm , medicine , nursing , software engineering , organic chemistry
A new program named “DARWIN” has been developed to perform docking calculations with proteins and other biological molecules. The program uses the Genetic Algorithm to optimize the molecule's conformation and orientation under the selective pressure of minimizing the potential energy of the complex. A unique feature of DARWIN is that it communicates with the molecular mechanics program CHARMM to make the energy calculations. A second important feature is its parallel interface, which allows simultaneous use of multiple stand‐alone copies of CHARMM to rapidly evaluate large numbers of potential solutions. This permits an “accuracy first” approach to docking, which avoids many of the common assumptions and shortcuts often made to reduce computation time. The method was applied to three protein‐carbohydrate complexes: the crystallographically determined structures of Concanavalin A and Fab Se155‐4; and a model structure for Fab ME36.1. Conformations close to the crystal structures were obtained with this approach, but some “false positive” solutions were also selected. Many of these could be eliminated by introducing different methods for simulating solvent effects. An effective screening method for docking a database of compounds to a single target enzyme using DARWIN is also presented. Proteins 2000;41:173–191. © 2000 Wiley‐Liss, Inc.