Since arriving at CABM and Rutgers in 1987 I have been pursuing structural studies of HIV-1 reverse transcriptase (RT) with dual goals of understanding the chemistry of this marvelous molecular machine at the atomic level, and of using the structures to facilitate the process of developing novel therapeutic agents targeting this enzyme.  I will review some of the variety of HIV-1 RT structures that have illuminated molecular mechanisms of catalysis, inhibition, and drug resistance.  Computational methods enabled by experimental structures from crystallography played a central role in the structure-based design cycle that led to the discovery of the HIV-1 RT non-nucleoside RT drugs rilpivirine and etravirine, both of which are resilient against drug-resistance mutations.   I am extremely grateful to my laboratory’s many gifted members whose dedicated efforts have made our work possible, and the many other colleagues worldwide who have contributed to these efforts and to understanding the many splendors of the amazing RT enzyme.  The talk will be given in honor of my friend and colleague Ronald Levy.

Successful drug design and broad insights from diverse structures of the multi-talented HIV-1 reverse transcriptase enzyme

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