Identification and mapping of small-molecule binding sites in proteins: computational tools for structure-based drug design

Farmaco. 2002 Mar;57(3):243-51. doi: 10.1016/s0014-827x(02)01211-9.

Abstract

The number of protein structures is currently increasing at an impressive rate. The growing wealth of data calls for methods to efficiently exploit structural information for medicinal and pharmaceutical purposes. Given the three-dimensional (3D) structure of a validated protein target, the identification of functionally relevant binding sites and the analysis ('mapping') of these sites with respect to molecular recognition properties are important initial tasks in structure-based drug design. To address these tasks, a variety of computational tools have been developed. Approaches to identify binding pockets include geometric analyses of protein surfaces, comparisons of protein structures, similarity searches in databases of protein cavities, and docking scans to reveal areas of high ligand complementarity. In the context of binding-site analysis, powerful data mining tools help to retrieve experimental information about related protein-ligand complexes. To identify interaction hot spots, various potential functions and knowledge-based approaches are available for mapping binding regions. The results may subsequently be used to guide virtual screenings for new ligands via pharmacophore searches or docking simulations.

Publication types

  • Review

MeSH terms

  • Artificial Intelligence
  • Binding Sites
  • Computer-Aided Design
  • Databases, Factual
  • Drug Design*
  • Ligands
  • Models, Chemical
  • Models, Molecular
  • Protein Conformation
  • Proteins / chemistry*
  • Quality Control
  • Reproducibility of Results
  • Sequence Homology
  • Structure-Activity Relationship

Substances

  • Ligands
  • Proteins