Login / Signup

Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors.

Tomas BastysVytautas GapsysHauke WalterEva HegerNadezhda T DonchevaRolf KaiserBert L de GrootOlga V Kalinina
Published in: Retrovirology (2020)
We demonstrate that estimating the effect of both binding pocket and distant mutations on inhibitor binding free energy using alchemical calculations can reproduce their effect on the experimentally measured [Formula: see text] values. We show that distant site mutations L76V and N88S affect the hydrogen bond network in the protease's active site, which offers an explanation for the indirect effect of these mutations on inhibitor binding. This work thus provides valuable insights on interplay between primary and background mutations and mechanisms how they affect inhibitor binding.
Keyphrases
  • dna binding
  • binding protein
  • lymph node
  • antiretroviral therapy
  • hiv positive
  • hiv infected
  • molecular dynamics simulations
  • smoking cessation
  • transcription factor
  • preterm birth
  • wild type