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Efficient electrostatic solvation model for protein‐fragment docking
Author(s) -
Majeux Nicolas,
Scarsi Marco,
Caflisch Amedeo
Publication year - 2000
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/1097-0134(20010201)42:2<256::aid-prot130>3.0.co;2-4
Subject(s) - fragment (logic) , solvation , docking (animal) , electrostatics , chemistry , implicit solvation , biophysics , biological system , chemical physics , computational chemistry , computer science , algorithm , biology , molecule , organic chemistry , medicine , nursing
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. © 2000 Wiley‐Liss, Inc.