Molecular and Coarse-Grained Simulations of Biomolecular Processes at the Petascale

千万亿级生物分子过程的分子和粗粒度模拟

• 批准号: 1811600
• 负责人: Gregory Voth
• 金额: $ 0.81万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1811600&HistoricalAwards=false
• 关键词: Molecular; Coarse; Grained; Simulations; Biomolecular

Computer simulations of biological systems can offer insights that are difficult or impossible to access with conventional experimental techniques, providing significant benefits for basic scientific research. However, the large range of characteristic time and length scales observed in biological processes makes the use of any single computational technique difficult. While atomic-resolution simulations can furnish a scientist with exquisite levels of detail, the sheer computational expense of these simulations sometimes presents a significant barrier for their application to large-scale biological problems. This project proposes to us coarse-grained (CG) molecular models to expand the reach of computer simulations to cellular scales. The project propose to integrate atomic-resolution and CG simulations to study a range of biologically relevant systems, in close collaboration with an international cohort of scientists from various experimental fields. This work will involve not only elucidating and explaining biomolecular processes, but also the development and dissemination of cutting-edge simulation software to the wider scientific community.The project aims to combine experimental data with cutting-edge computer simulations to investigate a number of important biomolecular systems. The systems of interest can be grouped into two main categories: critical stages of the viral lifecycles of HIV-1 and influenza, and studies of the actin filaments and microtubules of the cellular cytoskeleton. The project will develop an integrated pipeline which allows scientists to convert experimental data into computer models capable of investigating biomolecular processes at scales that are inaccessible to other approaches. While the results of atomic-scale simulations will clearly be important in and of themselves, they will also, in combination with experimental data, form the basis for generating and parameterizing rigorous UCG models. Results and predictions made by these models will be validated by close collaboration with experimental scientists, and used to suggest new directions in both the theoretical and experimental field. In addition to the development and deployment of advanced biomolecular simulation techniques, this proposal will also assist in the dissemination of the advances to the wider research community by the integration of the UCG model generation and simulation algorithms with the popular LAMMPS software.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.

生物系统的计算机模拟可以提供传统实验技术难以或不可能获得的见解，为基础科学研究提供显着的好处。 然而，在生物过程中观察到的大范围的特征时间和长度尺度使得使用任何单一计算技术都很困难。 虽然原子分辨率模拟可以为科学家提供精致的细节水平，但这些模拟的巨大计算成本有时会对其应用于大规模生物问题构成重大障碍。 该项目向我们提出了粗粒度（CG）分子模型，以将计算机模拟的范围扩展到细胞尺度。该项目提议与来自不同实验领域的国际科学家密切合作，整合原子分辨率和CG模拟来研究一系列生物相关系统。这项工作不仅涉及阐明和解释生物分子过程，还涉及开发尖端模拟软件并将其传播给更广泛的科学界。该项目旨在将实验数据与尖端计算机模拟相结合，以研究许多重要的生物分子系统。 感兴趣的系统可分为两大类：HIV-1 和流感病毒生命周期的关键阶段，以及细胞骨架的肌动蛋白丝和微管的研究。 该项目将开发一个集成管道，使科学家能够将实验数据转换为计算机模型，能够以其他方法无法达到的规模研究生物分子过程。虽然原子尺度模拟的结果本身显然很重要，但它们也将与实验数据相结合，形成生成和参数化严格 UCG 模型的基础。这些模型得出的结果和预测将通过与实验科学家的密切合作进行验证，并用于提出理论和实验领域的新方向。 除了开发和部署先进的生物分子模拟技术外，该提案还将通过将 UCG 模型生成和模拟算法与流行的 LAMMPS 软件相集成，帮助将这些进展传播到更广泛的研究界。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。