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.

这是一项行政补充请求，用于收购高性能 Dell，Inc.提供的计算(HPC)群集，用于包含1,664个CPU核心的13节点仪器 外加执行大规模并行分子动力学所需的低延迟网络 在Pi Alan Chen的父母NIH R35拨款中提出的模拟。已经取得了实质性的进展 在开发改进的RNA折叠模拟方法方面取得了进展，特别是一种新的2D- 复制交换分子动力学算法已经取得了令人印象深刻的初步结果 结果。然而，这种方法在生物相关的RNA上的应用目前是 由于PI现有仪器缺乏足够的计算能力而成为瓶颈。少年派的 现有仪器于2014年购买，由38个节点组成，采用双核、8核至强“Sandy “桥接”CPU。保修已于2019年到期，不再提供更换部件； 因此，这台仪器已经到了“生命的尽头”，即将作为个人退役 组件出现故障。这是一笔太大的费用，无法从父拨款中取代，而这 补充申请将使父母赠款的目标得以顺利完成。 以原子化细节分辨率3D折叠75-100个核苷酸的RNA，这将显著提高 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