ROAMING: SOLUTION STRUCTURE OF PNA AND DNA DOUBLE-HELICES WITH AND WITHOUT META

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目包括两个项目：项目1。本提案的目的是表征PNA/PNA，PNA/DNA和DNA/DNA双螺旋在溶液中的结构和动力学，具有不同的金属取代，并将所得结构与实验（晶体学和NMR）进行比较。所获得的结构将被用作输入半经验和从头电子转移（ET）的研究，以研究的顺序，结构，灵活性，溶剂和电荷对ET的影响。我们的长期目标是设计和合成基于金属-肽核酸（金属-PNA）双链体的分子系统，该系统允许精确控制电子流。项目2.我们的HIV-1逆转录酶（RT）研究的长期目标是设计新的抗HIV药物，对野生型和突变型RT更有效。拟议研究的目标是了解DAPYs作用的分子基础，这构成了新一代更有效的药物;以及RT和DAPYs之间的相互作用与上一代药物的不同。我们将通过研究HIV-1 RT和结合抑制剂之间的相互作用及其在分子动力学轨迹中的能量学来实现这一目标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.