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

Yakugaku Zasshi. 2011;131(10):1429-35. doi: 10.1248/yakushi.131.1429.
[Article in Japanese]

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.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Binding Sites
  • Biological Science Disciplines / methods*
  • Chemistry, Physical
  • Computational Biology / methods*
  • Drug Design*
  • Hydrophobic and Hydrophilic Interactions
  • Ligands
  • Multiprotein Complexes
  • Protein Binding
  • Protein Conformation
  • Proteins / chemistry*
  • Software*

Substances

  • Ligands
  • Multiprotein Complexes
  • Proteins