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Comparative molecular dynamics study of dimeric and monomeric forms of HIV-1 protease in ligand bound and unbound state
Abstract
Human immunodeficiency virus type 1 protease (HIV-1 PR) is a viral-encoded enzyme that forms a homodimer. HIV-1 PR is essential for replication and assembly of the virus and inactivation of HIV-1 PR enzyme causes production of immature, noninfectious viral particles and thus HIV-1 PR 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 and compared with FDA approved HIV-1 protease inhibitor Darunavir in complex with dimer and monomer form of HIV-1 PR. An apo form of HIV-1 protease as monomer and dimer form was also studied for 1000 ns of MD time in order to study response of protein to the ligand. MD results suggests that presence of ligand in dimer systems hinders the stability of HIV-1 protease enzyme and one monomer from dimer systems is dominant on other monomer in terms of interaction made with ligands. Monomer form of HIV-1 is more stable in ligand bound state as that of ligand unbound. We were able to trace functional residues as well as continuous motion of opening and closing (clapping) of flap region in HIV-1 PR (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.
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Details
- Category:
- Articles
- Type:
- artykuł w czasopiśmie wyróżnionym w JCR
- Published in:
-
GENERAL PHYSIOLOGY AND BIOPHYSICS
no. 36,
pages 141 - 154,
ISSN: 0231-5882 - Language:
- English
- Publication year:
- 2016
- Bibliographic description:
- Monikaben P., Umesh K.: Comparative molecular dynamics study of dimeric and monomeric forms of HIV-1 protease in ligand bound and unbound state// GENERAL PHYSIOLOGY AND BIOPHYSICS. -Vol. 36, nr. 2 (2016), s.141-154
- DOI:
- Digital Object Identifier (open in new tab) 10.4149/gpb_2016028
- Verified by:
- Gdańsk University of Technology
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