Studies Of The Hiv Protease And Dna Polymerase

Environmental Health Sciences

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Abstract

Summary of Work: The objective of these studies is to apply state of the art molecular simulation methodology as an adjunct to experimental structure-function studies of the HIV-1 Reverse Transcriptase. In this year we examined the influence of mutations at positions 89 and 154 on the rate of frameshifting and other template-slippage and primer-slippage mediated errors by the HIV-1 reverse transriptase. Although a detailed quantitative model has proven very difficult to obtain, largely due to lack of structural data pertaining to the translocation step of polymerization, we have provided a framework for discussion of the nature of the changes. We are continuing to work on the nature of sequence specific DNA structure and elasticity in order to explain sequence specific frameshifting and processivity results. Finally we began work modeling the effect of artificial amino acid changes at key positions in the RT polymerase finger domain to better understand the nature of the contacts with downstream DNA.