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

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重大好处。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的计算技术都很困难。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给它们在大规模生物学问题上的应用带来重大障碍。这个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。该项目建议与来自不同实验领域的国际科学家队列密切合作，整合原子分辨率和CG模拟，以研究一系列与生物相关的系统。这项工作不仅包括阐明和解释生物分子过程，还包括开发和向更广泛的科学界传播尖端模拟软件。该项目旨在将实验数据与尖端计算机模拟相结合，以研究一些重要的生物分子系统。感兴趣的系统可分为两大类：艾滋病毒-1和流感病毒生命周期的关键阶段，以及对细胞细胞骨架肌动蛋白细丝和微管的研究。该项目将开发一条综合管道，允许科学家将实验数据转换为计算机模型，从而能够在其他方法无法达到的规模上研究生物分子过程。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结合在一起，形成生成和参数化严格的UCG模型的基础。这些模型的结果和预测将通过与实验科学家的密切合作得到验证，并用于在理论和实验领域提出新的方向。除了开发和部署先进的生物分子模拟技术外，这项提议还将通过将UCG模型生成和模拟算法与流行的LAMMPS软件相结合，帮助将进展传播到更广泛的研究社区。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.