Target flexibility in molecular recognition

Biochim Biophys Acta. 2005 Dec 30;1754(1-2):221-4. doi: 10.1016/j.bbapap.2005.07.041. Epub 2005 Sep 12.

Abstract

Induced-fit effects are well known in the binding of small molecules to proteins and other macromolecular targets. Among other targets, protein kinases are particularly flexible proteins, so that such effects should be considered in attempts at structure-based inhibitor design for kinase targets. This paper outlines some recent progress in methods for including target flexibility in computational studies of molecular recognition. A focus is the "relaxed complex method," in which ligands are docked to an ensemble of conformations of the target, and the best complexes are re-scored to provide predictions of optimal binding geometries. Early applications of this method have suggested a new approach to the development of inhibitors of HIV-1 Integrase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Computer Simulation
  • Drug Design*
  • HIV Integrase / chemistry
  • Ligands
  • Models, Molecular*
  • Molecular Conformation
  • Protein Binding / drug effects
  • Protein Conformation
  • Proteins / chemistry*
  • Proteins / metabolism

Substances

  • Ligands
  • Proteins
  • HIV Integrase