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Highly accurate method for ligand‐binding site prediction in unbound state (apo) protein structures
Author(s) -
Morita Mizuki,
Nakamura Shugo,
Shimizu Kentaro
Publication year - 2008
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.22067
Subject(s) - ligand (biochemistry) , van der waals force , chemistry , binding site , protein ligand , binding energy , biophysics , molecule , biology , biochemistry , physics , receptor , organic chemistry , nuclear physics
This article describes a new method for predicting ligand‐binding sites of proteins. The method involves calculating the van der Waals interaction energy between a protein and probes placed on the protein surface, and then clustering the probes with attractive interaction to find the energetically most favorable locus. In 80% (28/35) of the test cases, the ligand‐binding site was successfully predicted on a ligand‐bound protein structure, and in 77% (27/35) was successfully predicted on an unbound structure. Our method was used to successfully predict ligand‐binding sites unaffected by induced‐fit as long as its scales were not very large, and it contributed to a significant improvement in prediction with unbound state protein structures. This represents a significant advance over conventional methods in detecting ligand‐binding sites on uncharacterized proteins. Moreover, our method can predict ligand‐binding sites with a narrower locus than those achieved using conventional methods. Proteins 2008. © 2008 Wiley‐Liss, Inc.