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Efficient electrostatic solvation model for protein-fragment docking.

N Majeux·M Scarsi·A Caflisch
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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. Proteins 2001;42:256-268.

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Binding SitesCaspase 1LigandsMitogen-Activated Protein KinasesModels, ChemicalModels, MolecularNuclear ProteinsPeptide FragmentsProtein BindingProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2Reproducibility of ResultsSoftware ValidationStatic ElectricityTacrolimus Binding Protein 1AThrombinp38 Mitogen-Activated Protein KinasesJournal ArticleResearch Support, Non-U.S. Gov't

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N Majeux, M Scarsi, A Caflisch. 2001-02-01. Efficient electrostatic solvation model for protein-fragment docking.. https://doi.org/10.1002/1097-0134(20010201)42%3A2%3C256%3A%3Aaid-prot130%3E3.0.co%3B2-4

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