Efficient electrostatic solvation model for protein-fragment docking

TitleEfficient electrostatic solvation model for protein-fragment docking
Publication TypeJournal Article
Year of Publication2001
AuthorsMajeux N., Scarsi M., Caflisch A.
JournalProteins: Structure, Function, and Bioinformatics
Volume42
Issue2
Pagination256-268
Date Published2001 Feb 1
Type of ArticleResearch Article
ISSN0887-3585
KeywordsBinding Sites, Caspase 1, Ligands, Mitogen-Activated Protein Kinases, Models, Chemical, Models, Molecular, Nuclear Proteins, p38 Mitogen-Activated Protein Kinases, Peptide Fragments, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Reproducibility of Results, Software Validation, Static Electricity, Tacrolimus Binding Protein 1A, Thrombin
Abstract

A method is presented for the fast evaluation of the binding energy of a protein-small molecule complex with electrostatic solvation. It makes use of a fast preprocessing step based on the assumption that the main contribution to electrostatic desolvation upon ligand binding originates from the displacement of the first shell of water molecules. For a rigid protein, the precomputation of the energy contributions on a set of grids allows the estimation of the energy in solution of about 300 protein-fragment binding modes per second on a personal computer. The docking procedure is applied to five rigid binding sites whose size ranges from 17 residues to a whole protein of 107 amino acids. Using a library of 70 mainly rigid molecules, known micromolar inhibitors or close analogs are docked and prioritized correctly. The docking based rank-ordering of the library requires about 5 h and is proposed as a complementary approach to structure-activity relationships by nuclear magnetic resonance.

DOI10.1002/1097-0134(20010201)42:2<256::AID-PROT130>3.0.CO;2-4
pubindex

0029

Alternate JournalProteins
PubMed ID11119650
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