Blind docking of pharmaceutically relevant compounds using RosettaLigand

TitleBlind docking of pharmaceutically relevant compounds using RosettaLigand
Publication TypeJournal Article
Year of Publication2009
AuthorsDavis, I. W., Raha K., Head M. S., & Baker D.
JournalProtein science
Volume18
Issue9
Pagination1998-2002
Date Published2009 Sep
ISSN1469-896X
KeywordsDrug Discovery, Ligands, Primary Publication, Protein Binding, Proteins, Software
Abstract

It is difficult to properly validate algorithms that dock a small molecule ligand into its protein receptor using data from the public domain: the predictions are not blind because the correct binding mode is already known, and public test cases may not be representative of compounds of interest such as drug leads. Here, we use private data from a real drug discovery program to carry out a blind evaluation of the RosettaLigand docking methodology and find that its performance is on average comparable with that of the best commercially available current small molecule docking programs. The strength of RosettaLigand is the use of the Rosetta sampling methodology to simultaneously optimize protein sidechain, protein backbone and ligand degrees of freedom; the extensive benchmark test described here identifies shortcomings in other aspects of the protocol and suggests clear routes to improving the method.

Alternate JournalProtein Sci.
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