A Critical Assessment of Docking Programs and Scoring Functions

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• 作者：Gregory L. Warren ; C. Webster Andrews ; Anna-Maria Capelli ; Brian Clarke ; Judith LaLonde ; Millard H. Lambert ; Mika Lindvall ; Neysa Nevins ; Simon F. Semus ; Stefan Senger ; Giovanna Tedesco ; Ian D. Wall
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：October 5, 2006
• 年：2006
• 卷：49
• 期：20
• 页码：5912 - 5931
• 全文大小：940K
• 年卷期：v.49,no.20(October 5, 2006)
• ISSN：1520-4804

文摘

Docking is a computational technique that samples conformations of small molecules in protein bindingsites; scoring functions are used to assess which of these conformations best complements the protein bindingsite. An evaluation of 10 docking programs and 37 scoring functions was conducted against eight proteinsof seven protein types for three tasks: binding mode prediction, virtual screening for lead identification,and rank-ordering by affinity for lead optimization. All of the docking programs were able to generateligand conformations similar to crystallographically determined protein/ligand complex structures for atleast one of the targets. However, scoring functions were less successful at distinguishing the crystallographicconformation from the set of docked poses. Docking programs identified active compounds from apharmaceutically relevant pool of decoy compounds; however, no single program performed well for all ofthe targets. For prediction of compound affinity, none of the docking programs or scoring functions madea useful prediction of ligand binding affinity.