Comparative molecular dynamics study of dimeric and monomeric forms of HIV-1 protease in ligand bound and unbound state

Gen Physiol Biophys. 2017 Apr;36(2):141-154. doi: 10.4149/gpb_2016028. Epub 2016 Dec 6.


Human immunodeficiency virus type 1 protease is a viral-encoded enzyme and it is essential for replication and assembly of the virus. Inactivation of HIV-1 protease causes production of immature, noninfectious viral particles and thus HIV-1 protease is an attractive target in anti-AIDS drug design. In our current work, we performed molecular dynamics (MD) calculations (500 ns) for two different ligands (COM5 - designed in our previous study, and Darunavir) and made effort to understand dynamics behaviour of our designed compound COM5. An apo form of HIV-1 protease as monomer and dimer form was also studied in order to analyze response of protein to the ligand. MD results suggest that presence of ligand in hinders the stability of HIV-1 protease and one monomer from dimer systems is dominant on other monomer in terms of interaction made with ligands. We were able to trace functional residues as well as continuous motion of opening and closing (clapping) of flap region in HIV-1 protease (apo form) during entire 1000 ns of MD simulation. COM5 showed almost similar behaviour towards HIV-1 protease enzyme as Darunavir and propose as promising lead compound for the development of new inhibitor for HIV-1 protease.

MeSH terms

  • Binding Sites
  • Darunavir / chemistry*
  • Enzyme Activation
  • HIV Protease / chemistry*
  • HIV Protease / drug effects
  • HIV Protease / ultrastructure*
  • HIV Protease Inhibitors / chemistry*
  • Models, Chemical*
  • Molecular Dynamics Simulation*
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization / drug effects


  • HIV Protease Inhibitors
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1
  • Darunavir