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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本提案由两个项目组成：项目1.本提案的目标是表征具有不同金属取代的PNA/PNA、PNA/DNA和DNA/DNA双螺旋在溶液中的结构和动力学，并将所得到的结构与实验结构(结晶学和核磁共振)进行比较。所获得的结构将被用作半经验和从头算电子转移(ET)研究的输入，以研究序列、结构、柔性、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)双链的分子系统，这使得电子流动能够得到精确的控制。我们HIV-1逆转录酶(RT)研究的长期目标是设计新的抗HIV药物，更有效地对抗野生型和突变型RT。拟议研究的目的是了解DAPY的分子作用基础，它构成了新一代更有效的药物；以及RT和DAPY之间的相互作用如何与前一代药物不同。我们将通过研究HIV-1RT和结合抑制物之间的相互作用以及它们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.