Understanding the basis of resistance in the irksome Lys103Asn HIV-1 reverse transcriptase mutant through targeted molecular dynamics simulations

J Am Chem Soc. 2004 Dec 1;126(47):15386-7. doi: 10.1021/ja045409t.

Abstract

Results of targeted molecular dynamics simulations confirm the existence of a higher energy barrier for creation of the pocket where non-nucleoside reverse transcriptase inhibitors bind in the K103N mutant enzyme relative to wild-type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / metabolism
  • Anti-HIV Agents / pharmacology*
  • Binding Sites
  • Drug Resistance, Viral
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / genetics*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Hydrogen Bonding
  • Kinetics
  • Models, Molecular
  • Mutation*
  • Protein Conformation
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / metabolism
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Thermodynamics

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase