Human Immunodeficiency Virus Type-1 (HIV-1) is a widespread viral pathogen that causes Acquired Immunodeficiency Syndrome (AIDS) in humans. HIV-1 protease, a primary target of anti-AIDS treatment, is responsible for regulation of the post-translational processing of pre-viral gag and gag-pol protein complexes during the viral budding step of the HIV life cycle. This post-translational processing allows the immature virus to transform into a mature virion. We seek to determine whether novel HIV-1 protease inhibitors based on the polyhedral oligomeric silsesquioxane (POSS) scaffold exhibit in-silico binding affinities favorable enough to warrant experimental evaluation. POSS is a cage-like structure composed of oxygen and silicon atoms that allow for specific orientation of high-affinity ligand arms in the binding pocket of HIV-1 protease. We have performed molecular dynamics (MD) simulations on the wide-open, opened, semi-opened and closed apo conformations of HIV-1 protease using the AMBER 16 software suite. Various POSS derivatives will be docked to stabilized apo conformations for subsequent MD simulation. A deeper understanding of the inhibition of HIV-1 protease with POSSdderivatives will potentially lead to the development of new anti-AIDS drugs.

Evaluating the binding of a novel POSS-based HIV protease inhibitor drug

2019 Spring National Meeting

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