This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This proposal consists of two projects: Project 1. The objectives of the present proposal are to characterize the structure and dynamics of PNA/PNA, PNA/DNA and DNA/DNA double helices in solution, with different metal substitutions, and to compare the resulting structures to experimental (crystallographic and NMR) ones. The obtained structures will be used as input to semi-empirical and ab initio electron transfer (ET) studies, in order to study the effect of sequence, structure, flexibility, solvent and charge on ET. Our long-term goal is to design and synthesize molecular systems based on metal-peptide nucleic acids (metal-PNA) duplexes, which allow the precise control of electronic flow. Project 2. The long term goal of our HIV-1 reverse transcriptase (RT) research is to design new anti-HIV drugs, more effective against wild-type and mutant RT. The objectives of the proposed research are to understand the molecular basis of action of DAPYs, which constitute a new generation of more effective drugs; and how the interactions between RT and DAPYs differ from previous generation drugs. We will achieve this objective by studying the interactions between HIV-1 RT and bound inhibitors, and their energetics, during molecular dynamics trajectories.
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