Maximum common binding modes (MCBM): consensus docking scoring using multiple ligand information and interaction fingerprints

Journal of Chemical Information and Modeling
Steffen RennerFabian Mörchen

Abstract

Improving the scoring functions for small molecule-protein docking is a highly challenging task in current computational drug design. Here we present a novel consensus scoring concept for the prediction of binding modes for multiple known active ligands. Similar ligands are generally believed to bind to their receptor in a similar fashion. The presumption of our approach was that the true binding modes of similar ligands should be more similar to each other compared to false positive binding modes. The number of conserved (consensus) interactions between similar ligands was used as a docking score. Patterns of interactions were modeled using ligand receptor interaction fingerprints. Our approach was evaluated for four different data sets of known cocrystal structures (CDK-2, dihydrofolate reductase, HIV-1 protease, and thrombin). Docking poses were generated with FlexX and rescored by our approach. For comparison the CScore scoring functions from Sybyl were used, and consensus scores were calculated thereof. Our approach performed better than individual scoring functions and was comparable to consensus scoring. Analysis of the distribution of docking poses by self-organizing maps (SOM) and interaction fingerprints confirmed tha...Continue Reading

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Citations

Jan 11, 2012·Journal of Computer-aided Molecular Design·Oliver KorbThomas E Exner
Apr 30, 2013·Journal of Chemical Information and Modeling·Bingjie Hu, Markus A Lill
Oct 12, 2012·Advances and Applications in Bioinformatics and Chemistry : AABC·Alexey B MantsyzovGildas Bertho
May 11, 2011·Future Medicinal Chemistry·Steffen RennerEdgar Jacoby
Jan 19, 2012·Chemical Biology & Drug Design·Jiaying Sun, Hu Mei
Sep 1, 2015·Journal of Chemical Information and Modeling·Sheng-You HuangYi Pan
Sep 29, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ming HongYibin Feng
Feb 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ming HongWeiwei Xing
Aug 2, 2018·Molecular Informatics·Alexandre BorgesRosangela da Silva de Laurentiz
May 3, 2018·Nucleic Acids Research·Priyanka BanerjeeRobert Preissner
May 5, 2011·Journal of Computational Chemistry·Trent E BaliusRobert C Rizzo
May 19, 2009·Journal of Chemical Information and Modeling·Pablo Englebienne, Nicolas Moitessier
Apr 30, 2008·Journal of Chemical Information and Modeling·Sebastian RadestockSteffen Renner
Aug 29, 2009·Journal of Chemical Information and Modeling·Izhar Wallach, Ryan Lilien
Aug 4, 2011·Journal of Chemical Information and Modeling·Richard D SmithHeather A Carlson

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