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

Hassan, S.; Srikakulam, S.K.; Yuvaraj, C.; Thangam, M.; Muthukumar, S.; Gayathri Devi, P.K.; Hanna, L.E.

Proteins; 2018; 86(9): 990-1000.

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.

Keywords: HIV, protease, principal component analysis, RMSD, structural analysis

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