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An iterative knowledge‐based scoring function to predict protein–ligand interactions: II. Validation of the scoring function
Author(s) -
Huang ShengYou,
Zou Xiaoqin
Publication year - 2006
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20505
Subject(s) - virtual screening , binding affinities , protein ligand , ligand (biochemistry) , function (biology) , docking (animal) , quantitative structure–activity relationship , test set , affinities , computational biology , chemistry , computer science , computational chemistry , machine learning , stereochemistry , molecular dynamics , biology , biochemistry , genetics , medicine , nursing , receptor
We have developed an iterative knowledge‐based scoring function (ITScore) to describe protein–ligand interactions. Here, we assess ITScore through extensive tests on native structure identification, binding affinity prediction, and virtual database screening. Specifically, ITScore was first applied to a test set of 100 protein–ligand complexes constructed by Wang et al. (J Med Chem 2003, 46, 2287), and compared with 14 other scoring functions. The results show that ITScore yielded a high success rate of 82% on identifying native‐like binding modes under the criterion of rmsd ≤2 Å for each top‐ranked ligand conformation. The success rate increased to 98% if the top five conformations were considered for each ligand. In the case of binding affinity prediction, ITScore also obtained a good correlation for this test set (R = 0.65). Next, ITScore was used to predict binding affinities of a second diverse test set of 77 protein–ligand complexes prepared by Muegge and Martin (J Med Chem 1999, 42, 791), and compared with four other widely used knowledge‐based scoring functions. ITScore yielded a high correlation of R 2 = 0.65 (or R = 0.81) in the affinity prediction. Finally, enrichment tests were performed with ITScore against four target proteins using the compound databases constructed by Jacobsson et al. (J Med Chem 2003, 46, 5781). The results were compared with those of eight other scoring functions. ITScore yielded high enrichments in all four database screening tests. ITScore can be easily combined with the existing docking programs for the use of structure‐based drug design. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006