Modelling the binding of HIV-reverse transcriptase and nevirapine

An assessment of quantum mechanical and force field approaches and predictions of the effect of mutations on binding

Rajesh K. Raju, Neil A. Burton, Ian H. Hillier

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The importance of the intermolecular interactions which contribute to the binding of HIV-1 RT with the NNRTI inhibitor, nevirapine (NVP), has been studied using quantum mechanical and molecular simulation methods. A range of computational methods, including density functional theory with empirical dispersion corrections, have been employed and show that although π-π stacking interactions are important, the combined effect of a number of C-H/π interactions provides a significant contribution to the binding. The AMBER empirical force-field has been shown to be particularly effective to describe the interactions in this case; MM-GBSA free-energy methods were subsequently used to explore the effects on binding with several known mutations of HIV-1 RT. The relative affinities from the mutation simulations are shown to be in good agreement with experimental data allowing the causes of the binding changes to be discussed.

Original languageEnglish
Pages (from-to)7117-7125
Number of pages9
JournalPhysical Chemistry Chemical Physics
Volume12
Issue number26
DOIs
Publication statusPublished - 14 Jul 2010
Externally publishedYes

Fingerprint

HIV Reverse Transcriptase
Nevirapine
human immunodeficiency virus
mutations
Computational methods
field theory (physics)
Free energy
Density functional theory
Mutation
HIV-1
predictions
interactions
energy methods
inhibitors
affinity
simulation
free energy
density functional theory
causes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Physics and Astronomy(all)
  • Medicine(all)

Cite this

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