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

漫游：带或不带 Meta 的 PNA 和 DNA 双螺旋的解结构

• 批准号: 7723362
• 负责人: MARCELA MADRID
• 金额: $ 0.05万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723362
• 关键词: Anti-HIV Agents; Binding; Charge; Computer Retrieval of Information on Scientific Projects Database; Drug Interactions; Electron Transport; Electronics; Funding; Generations; Goals; Grant; HIV-1 Reverse Transcriptase; Helix (Snails); Institution; Metals; Molecular; Peptide Nucleic Acids; Pharmaceutical Preparations; Pliability; RNA-Directed DNA Polymerase; Research; Research Personnel; Resources; Solutions; Solvents; Source; Structure; System; United States National Institutes of Health; base; design; ear helix; inhibitor/antagonist; molecular dynamics; mutant

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该提案由两个项目组成：项目1。本提案的目标是表征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，并将结果结构与实验性（晶体学和NMR）进行比较。所获得的结构将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，柔韧性，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，从而可以精确控制电子流。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，对野生型和突变体RT更有效。拟议的研究的目标是了解DAPY的作用的分子基础，DAPY构成了新一代更有效的药物。 RT和DAPYS之间的相互作用与上一代药物有何不同。我们将通过研究分子动力学轨迹期间HIV-1 RT与结合抑制剂及其能量学之间的相互作用来实现这一目标。