[Development and validation of programs for ligand-binding-pocket search]

Abstract

Searching for the ligand-binding pockets of proteins plays an important role in structure-based drug design (SBDD), which is based on knowledge of the three-dimensional structures of target proteins. In SBDD, small molecules that can interact with the target protein are designed. SBDD methods require the identification of ligand-binding pockets, in which ligand molecules interact with protein atoms. The computer programs for the detection of ligand-binding pockets are categorized into two types: one is programs using only geometric properties; and the other is programs using the physicochemical properties of proteins as well as geometry. This paper describes the development and evaluation of a program for ligand-binding pocket search. The program HBOP (Hydropho Bicity On a Protein) searches for ligand-binding pockets using hydrophobic potentials derived from experimentally determined functions. This is based on the fact that hydrophobicity plays a significant role in protein-ligand binding. The results of evaluation indicate that programs using physicochemical properties can discover actual ligand-binding pockets more efficiently than those using only geometric properties.