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Architectural Repertoire of Ligand‐Binding Pockets on Protein Surfaces
Author(s) -
Weisel Martin,
Kriegl Jan M.,
Schneider Gisbert
Publication year - 2010
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200900604
Subject(s) - druggability , ligand (biochemistry) , computational biology , identification (biology) , network topology , topology (electrical circuits) , binding site , protein ligand , chemistry , resolution (logic) , drug discovery , computer science , biology , receptor , biochemistry , artificial intelligence , engineering , gene , botany , operating system , electrical engineering
Abstract Knowledge of the three‐dimensional structure of ligand binding sites in proteins provides valuable information for computer‐assisted drug design. We present a method for the automated extraction and classification of ligand binding site topologies, in which protein surface cavities are represented as branched frameworks. The procedure employs a growing neural gas approach for pocket topology assignment and pocket framework generation. We assessed the structural diversity of 623 known ligand binding site topologies based on framework cluster analysis. At a resolution of 5 Å only 23 structurally distinct topology groups were formed; this suggests an overall limited structural diversity of ligand‐accommodating protein cavities. Higher resolution allowed for identification of protein‐family specific pocket features. Pocket frameworks highlight potentially preferred modes of ligand–receptor interactions and will help facilitate the identification of druggable subpockets suitable for ligand affinity and selectivity optimization.