Exploring the energetic basis of binding of currently used drugs against HIV-1 subtype CRF01_AE protease via molecular dynamics simulations.

Journal of Biomolecular Structure & Dynamics
Md Fulbabu SkParimal Kar

Abstract

Non-B strains cause nearly 90% of the worldwide human immunodeficiency virus (HIV) infections. At the same time, the protease inhibitors (PIs) were designed for subtype B. Therefore, the use of PIs in the non-B subtype context requires further investigation. Herein, we have investigated the effectiveness of currently used four PIs, namely atazanavir, darunavir, lopinavir, and tipranavir against subtype CRF01_AE (PRCRF) by employing the MD/MMPBSA (molecular dynamics/molecular mechanics Poisson-Boltzmann surface area) scheme. Our investigation reveals that tipranavir is the most potent inhibitor against PRCRF while the other three PIs display a similar binding affinity. The energetic penalty arises due to the desolvation of polar groups always disfavor the association between PRCRF and PI, and this contribution is the least in the case of tipranavir/PRCRF compared to the other three PI-PRCRF complexes resulting in a better binding affinity for tipranavir. Further, it is revealed that the primary interaction controlling the binding of inhibitors with PRCRF is the van der Waals forces. The dynamic cross-correlation map and principal component analysis show that the anti-correlated motion at the flap region of PRCRF is diminished af...Continue Reading

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Citations

May 31, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mahmudul HasanMd Bashir Uddin
Jul 28, 2021·Chemometrics and Intelligent Laboratory Systems : an International Journal Sponsored by the Chemometrics Society·Vijay H MasandMagdi E A Zaki
Jul 18, 2020·Journal of Biomolecular Structure & Dynamics·Shruti KoulgiRajendra Joshi

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