On the use of molecular dynamics receptor conformations for virtual screening

Methods Mol Biol. 2012:819:93-103. doi: 10.1007/978-1-61779-465-0_7.

Abstract

Receptors are inherently dynamic and this flexibility is important to consider when constructing a model of molecular association. Conformations from molecular dynamics simulations, a well-established method for examining protein dynamics, can be used in virtual screening to account for flexibility in structure-based drug discovery. Different receptor configurations influence docking results. Molecular dynamics simulations can provide snapshots that improve virtual screening predictive power over known crystal structures, most likely as a result of sampling more relevant receptor conformations. Here we highlight some details and nuances of using such snapshots and evaluating them for predictive performance.

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.

MeSH terms

  • Crystallography, X-Ray
  • Drug Evaluation, Preclinical / methods*
  • Models, Molecular
  • Molecular Dynamics Simulation*
  • Protein Conformation
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / metabolism
  • Software
  • User-Computer Interface*

Substances

  • Receptors, Cell Surface