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Multipose binding in molecular docking.

ABSTRACT: Molecular docking has been extensively applied in virtual screening of small molecule libraries for lead identification and optimization. A necessary prerequisite for successful differentiation between active and non-active ligands is the accurate prediction of their binding affinities in the complex by use of docking scoring functions. However, many studies have shown rather poor correlations between docking scores and experimental binding affinities. Our work aimed to improve this correlation by implementing a multipose binding concept in the docking scoring scheme. Multipose binding, i.e., the property of certain protein-ligand complexes to exhibit different ligand binding modes, has been shown to occur in nature for a variety of molecules. We conducted a high-throughput docking study and implemented multipose binding in the scoring procedure by considering multiple docking solutions in binding affinity prediction. In general, improvement of the agreement between docking scores and experimental data was observed, and this was most pronounced in complexes with large and flexible ligands and high binding affinities. Further developments of the selection criteria for docking solutions for each individual complex are still necessary for a general utilization of the multipose binding concept for accurate binding affinity prediction by molecular docking.

SUBMITTER: Atkovska K

PROVIDER: S-EPMC3958872 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Multipose binding in molecular docking.

Atkovska Kalina K Samsonov Sergey A SA Paszkowski-Rogacz Maciej M Pisabarro M Teresa MT

International journal of molecular sciences 20140214 2

Molecular docking has been extensively applied in virtual screening of small molecule libraries for lead identification and optimization. A necessary prerequisite for successful differentiation between active and non-active ligands is the accurate prediction of their binding affinities in the complex by use of docking scoring functions. However, many studies have shown rather poor correlations between docking scores and experimental binding affinities. Our work aimed to improve this correlation ...[more]

PMID: 24534807

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Dataset Information

Multipose binding in molecular docking.

Publications

Multipose binding in molecular docking.

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