Exploring the conformational landscapes of HIV protease structural ensembles using principal component analysis

Proteins. 2018 Sep;86(9):990-1000. doi: 10.1002/prot.25534. Epub 2018 Sep 17.

Abstract

HIV protease, an essential enzyme for viral particle maturation, is an important drug target of HIV. Its structural conformation is a key determinant of both biological function as well as efficient binding of protease inhibitor molecules. In the present study we analyzed 471 crystal structures of HIV-1 protease to understand the conformational changes induced by mutations or binding of various ligands and substrates. We performed principal component analysis on the ensembles of the HIV-1 protease structures to explore the conformational landscapes. The study identified structural differences between drug resistant and drug sensitive protease structures. Conformational changes were identified in the A and B chains of homo-dimeric HIV protease structures having different combinations of mutations, and also rigidity in the binding conformation of HIV drugs within the active site of the protein.© 2018 Wiley Periodicals, Inc.

Keywords: HIV; RMSD; principal component analysis; protease; structural analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Protein
  • Drug Resistance, Viral
  • HIV Protease / chemistry*
  • HIV Protease / genetics
  • HIV Protease Inhibitors / chemistry*
  • HIV-1 / enzymology*
  • Humans
  • Ligands
  • Models, Molecular*
  • Mutation
  • Principal Component Analysis*
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization

Substances

  • HIV Protease Inhibitors
  • Ligands
  • HIV Protease