Enhancing the accuracy of virtual screening: molecular dynamics with quantum-refined force fields

J Comput Aided Mol Des. 2004 Dec;18(12):773-84. doi: 10.1007/s10822-004-7881-6. Epub 2005 Jun 27.

Abstract

A methodology aimed at improving the accuracy of current docking-scoring procedures is proposed, and validated through detailed tests of its performance in predicting the activity of HIV-1 protease inhibitors. This methodology is based on molecular dynamics simulations using a force field whose effective charges are refined by means of a novel procedure that relies on quantum-mechanical calculations and preserves the internal consistency of the parameterization scheme.

MeSH terms

  • Drug Design*
  • Drug Evaluation, Preclinical / methods*
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacology
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • Ligands
  • Molecular Structure
  • Proteins / chemistry
  • Quantum Theory
  • Thermodynamics
  • User-Computer Interface*

Substances

  • HIV Protease Inhibitors
  • Ligands
  • Proteins