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RAPID: Computational studies of the structural dynamics, function and inhibition of the SARS-CoV-2 coronavirus spike protein

RAPID：SARS-CoV-2 冠状病毒刺突蛋白的结构动力学、功能和抑制的计算研究

基本信息

批准号：
2028443
负责人：
Ioan Andricioaei
金额：
$ 19.96万
依托单位：
University of California-Irvine
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-15 至 2022-10-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2028443&HistoricalAwards=false
关键词：
RAPID Computational studies structural dynamics

项目摘要

This NSF Rapid response Research (RAPID) project funded by the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences will support a project that is aimed to thoroughly characterize the dynamical transitions the coronavirus membrane-surface spike (S) glycoprotein by computer simulations both locally upon receptor/antigen binding and globally upon fusion. The spike protein binds a receptor on the surface of the cell and undergoes a long-time, large-scale conformational transition that triggers fusion. This project will emphasize the role of deploying recent advances in enhanced sampling simulations to obtaining thermal and kinetic averages that make valid connection to the timescales of the experiments. Lessons learned from this project will not only improve the understanding of the structure and dynamics of the SARS-CoV-2 spike protein but will deepen the molecular biophysics understanding of viruses in general. In addition to direct scientific insights, the project will impact the education of graduate, undergraduate, and middle-school students, inform a large research community, and engage the broader public through outreach activities.The 2019 novel coronavirus, identified as the cause for the pneumonia pathology reported in Wuhan, spread quickly and became a global pandemic. The project will employ novel computational techniques grounded in rigorous statistical mechanics to understand the role of the dynamics for the function of the spike protein, the key macromolecular component whose structural rearrangements are responsible for antibody neutralization and entry to the host cell for infection. In its recently released prioritization recommendation, the World Health Organization stressed the need for antigens to target this spike protein. This project will help in the interpretation of biochemical measurements on neutralization sensitivity, receptor reactivity, and immunity response changes due to widespread infection.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

由分子和细胞生物科学部分子生物物理学计划资助的NSF快速反应研究（RAPID）项目将支持一个项目，该项目旨在通过计算机模拟局部受体/抗原结合和融合后的全局，彻底表征冠状病毒膜表面刺突（S）糖蛋白的动态转变。刺突蛋白结合细胞表面的受体，并经历长时间、大规模的构象转变，从而触发融合。该项目将强调部署最新进展的作用，在增强采样模拟，以获得热和动力学的平均值，使有效的连接到实验的时间尺度。从该项目中吸取的经验教训不仅将提高对SARS-CoV-2刺突蛋白的结构和动力学的理解，而且将加深对病毒的分子生物物理学理解。除了直接的科学见解，该项目还将影响研究生、本科生和中学生的教育，为大型研究社区提供信息，并通过外展活动吸引更广泛的公众。2019年新型冠状病毒被确定为武汉报告的肺炎病理学原因，迅速传播并成为全球大流行病。该项目将采用基于严格统计力学的新型计算技术，以了解刺突蛋白功能的动力学作用，刺突蛋白是关键的大分子组分，其结构重排负责抗体中和和进入宿主细胞进行感染。在其最近发布的优先级建议中，世界卫生组织强调需要抗原来靶向这种刺突蛋白。该项目将有助于解释由于广泛感染引起的中和敏感性、受体反应性和免疫反应变化的生化测量结果。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。