Thermodynamically Calibrated RNA Simulations to Decode Mechanisms of RNAMolecular Recognition

通过热力学校准的 RNA 模拟来解码 RNA 分子识别机制

• 批准号: 10797206
• 负责人: Alan Austin Chen
• 金额: $ 24.45万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT ALBANY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10797206
• 关键词: 3-Dimensional; Administrative Supplement; Algorithms; Biomedical Research; Calibration; Computer Simulation; Disease; Goals; Grant; High Performance Computing; Individual; Methods; Molecular; Parents; RNA; RNA Folding; Resolution; Structure-Activity Relationship; Thermodynamics; United States National Institutes of Health; cluster computing; design; end of life; improved; in silico; instrument; molecular dynamics; novel; parent grant; simulation; therapeutic RNA

This is an administrative supplement request for the acquisition of a High-Performance Computing (HPC) cluster from Dell, Inc. for a 13 nodes instrument containing 1,664 CPU cores plus low-latency networking necessary to carry out the massively parallel molecular dynamics simulations proposed in PI Alan Chen’s parent NIH R35 grant. Substantial progress has been made in developing improved simulation methods for RNA folding, in particular, a novel 2D- Replica-Exchange-Molecular Dynamics algorithm which has yielded impressive preliminary results. However, the application of this method to biologically relevant RNAs is currently bottlenecked by the lack of sufficient computing power of the PI’s existing instrument. The PI’s existing instrument, purchased in 2014, consists of 38 nodes with dual, 8-core Xeon “Sandy Bridge” CPUs. The warranty expired in 2019, and replacement parts are no longer available; therefore, this instrument has reached “end of life” and is being retired as individual components fail. This is too large an expense to replace from the parent grant, and this supplement request would enable the successful completion of the parent grant’s goal of high- resolution 3D folding of 75-100 nt RNAs in atomistic detail, which would significantly advance biomedical research.

这是获得高性能的行政补充要求 Dell，Inc。的计算（HPC）集群，用于13个节点仪器，其中包含1,664个CPU核心 加上进行大规模平行分子动力学所需的低延迟网络 Pi Alan Chen的父母NIH R35 Grant提出了模拟。很大的进步已经 在开发改进的RNA折叠的改进的模拟方法中，特别是一种新型的2D- 复制 - 交换 - 分子动力学算法，该算法产生了令人印象深刻的初步 结果。但是，该方法在生物学相关的RNA中的应用目前是 由于缺乏PI现有仪器的足够计算能力而瓶颈。 PI的 2014年购买的现有仪器包括38个节点，带有双重，8核Xeon“ Sandy 桥梁” CPU。保修于2019年到期，替换零件不再可用； 因此，该工具已达到“生命的尽头”，并已退休 组件失败。这太大了，无法取代父母赠款，这是 补充请求将使父母赠款的高级目标成功完成 分辨率3D折叠75-100 nt RNA的原子细节，这将大大提高 生物医学研究。

项目成果

Structural and Binding Effects of Chemical Modifications on Thrombin Binding Aptamer (TBA).

• DOI: 10.3390/molecules26154620
• 发表时间: 2021-07-30
• 期刊: Molecules (Basel, Switzerland)
• 作者: Valsangkar V;Vangaveti S;Lee GW;Fahssi WM;Awan WS;Huang Y;Chen AA;Sheng J
• 通讯作者: Sheng J