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Flexible relaxation of rigid‐body docking solutions
Author(s) -
Król Marcin,
Tournier Alexander L.,
Bates Paul A.
Publication year - 2007
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/prot.21391
Subject(s) - docking (animal) , intermolecular force , searching the conformational space for docking , molecular dynamics , chemistry , force field (fiction) , interaction energy , rigid body , cluster (spacecraft) , chemical physics , protein–ligand docking , computational chemistry , crystallography , energy landscape , macromolecule , biological system , molecule , protein structure , computer science , physics , virtual screening , artificial intelligence , classical mechanics , biology , medicine , biochemistry , nursing , organic chemistry , programming language
Molecular Dynamics (MD) simulations have been performed on a set of rigid‐body docking poses, carried out over 25 protein–protein complexes. The results show that fully flexible relaxation increases the fraction of native contacts (NC) by up to 70% for certain docking poses. The largest increase in the fraction of NC is observed for docking poses where anchor residues are able to sample their bound conformation. For each MD simulation, structural snap‐shots were clustered and the centre of each cluster used as the MD‐relaxed docking pose. A comparison between two energy‐based scoring schemes, the first calculated for the MD‐relaxed poses, the second for energy minimized poses, shows that the former are better in ranking complexes with large hydrophobic interfaces. Furthermore, complexes with large interfaces are generally ranked well, regardless of the type of relaxation method chosen, whereas complexes with small hydrophobic interfaces remain difficult to rank. In general, the results indicate that current force‐fields are able to correctly describe direct intermolecular interactions between receptor and ligand molecules. However, these force‐fields still fail in cases where protein–protein complexes are stabilized by subtle energy contributions. Proteins 2007. © 2007 Wiley‐Liss, Inc.