Binary image representation of a ligand binding site: its application to efficient sampling of a conformational ensemble

Background: Modelling the ligand binding site of a protein is an important component of understanding proteinligand interactions and is being actively studied. Even if the side chains are restricted to rotamers, a set of commonlyobserved low-energy conformations, the exhaustive combinatorial search of ligand binding site conformers is known as NP-hard. Here we propose a new method, ROTAIMAGE, for modelling the plausible conformers for the ligand binding site given a fixed backbone structure. Results: ROTAIMAGE includes a procedure of selecting ligand binding site residues, exhaustively searching rotameric conformers, clustering them by dissimilarities in pocket shape, and suggesting a representative conformer per cluster. Prior to the clustering, the list of conformers generated by exhaustive search can be reduced by pruning the conformers that have near identical pocket shapes, which is done using simple bit operations. We tested our approach by modelling the active-site inhibitor bi...

• Type: Journal
• Year: 2010
• Where: BMCBI
• Authors: Edon Sung, Sangsoo Kim, Whanchul Shin
• Keywords: BMCBI 2010, Conformers, Ligand, Pocket