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Evaluation of the F LEX X incremental construction algorithm for protein–ligand docking
Author(s) -
Kramer Bernd,
Rarey Matthias,
Lengauer Thomas
Publication year - 1999
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/(sici)1097-0134(19991101)37:2<228::aid-prot8>3.0.co;2-8
Subject(s) - docking (animal) , dock , searching the conformational space for docking , computer science , protein–ligand docking , algorithm , virtual screening , artificial intelligence , chemistry , protein structure , molecular dynamics , biochemistry , computational chemistry , medicine , nursing
We report on a test of F LEX X, a fully automatic docking tool for flexible ligands, on a highly diverse data set of 200 protein–ligand complexes from the Protein Data Bank. In total 46.5% of the complexes of the data set can be reproduced by a F LEX X docking solution at rank 1 with an rms deviation (RMSD) from the observed structure of less than 2 Å. This rate rises to 70% if one looks at the entire generated solution set. F LEX X produces reliable results for ligands with up to 15 components which can be docked in 80% of the cases with acceptable accuracy. Ligands with more than 15 components tend to generate wrong solutions more often. The average runtime of F LEX X on this test set is 93 seconds per complex on a SUN Ultra‐30 workstation. In addition, we report on “cross‐docking” experiments, in which several receptor structures of complexes with identical proteins have been used for docking all cocrystallized ligands of these complexes. In most cases, these experiments show that F LEX X can acceptably dock a ligand into a foreign receptor structure. Finally we report on screening runs of ligands out of a library with 556 entries against ten different proteins. In eight cases F LEX X is able to find the original inhibitor within the top 7% of the total library. Proteins 1999;37:228–241. ©1999 Wiley‐Liss, Inc.