Coarse-graining complex interaction landscapes

加州大学圣巴巴拉分校的M. Scott Shell获得了化学学部化学理论、模型和计算方法项目的奖励，为系统粗粒度分析开发了基础广泛的算法。分子世界的计算机模拟是一种成熟的、宝贵的工具，用于理解原子运动和相互作用的协调如何产生生物学、材料、流体混合物等中观察到的特性。模拟也可能为设计新的合成分子提供新的实验方向。即使是在最短的时间内（百万分之一秒）对分子中的每个原子进行建模，在计算上也是非常昂贵的。这一费用严重限制了模拟的复杂性。谢尔博士及其同事开发了一种方法，可以自动识别模拟中不必要的原子细节。这些不必要的细节被需要更少计算的“粗粒度”模型所取代。反过来，这些粗糙的模型允许在更大的尺度上进行模拟。这种能力带来了新的问题和研究体系。该项目通过创建强大的方法来发展这一基本方法，以保持高度粗糙的模型的高精度，并应用新技术来理解肽基材料。该项目为不同层次的学生提供了教育机会，包括那些来自代表性不足群体的学生的参与。谢尔教授指导本科生研究人员，并参与了几个校园范围内的多样性倡议，这些倡议有助于UCSB加州纳米系统研究所的专业发展和研究培训计划。该团队制定策略，以改善在理论和计算研究方面招收女学生的情况。由谢尔博士协调的年度研讨会将杰出的女性研究人员带到校园，为本科生、研究生和博士后树立榜样。虽然粗粒度方法近年来得到了大力的研究，但主要的实际和概念障碍仍然存在，这些障碍损害了粗粒度（CG）模型的准确性、可移植性和自动化，从而限制了这些非常重要的建模方法的总体可靠性。该项目利用壳牌集团开发的相对熵框架来创建解决这些限制的通用新策略。这些新方法植根于严格的统计力学理论和最先进的分子模拟技术。具体来说，该项目创建了强大的策略，可以高效、准确地建模复杂的、跨状态条件、化学和系统的多体CG交互，并在自下而上的CG策略中无缝地包括外部约束（如实验信息）。作为该技术的应用，本工作开发了下一代通用但序列敏感的CG肽模型，适用于理解和预测新兴杂化聚合物-肽材料中的超分子自组装。该奖项反映了美国国家科学基金会的法定使命，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。

M. Scott Shell of the University of California Santa Barbara is supported by an award from the Chemical Theory, Models, and Computational Methods program in the Chemistry Division to develop broad-based algorithms for systematic coarse-graining. Computer simulations of the molecular world are an established and invaluable tool for understanding how the concert of atomic motions and interactions gives rise to observed properties in biology, materials, fluid mixtures, etc. Simulations may also suggest novel experimental directions for the design of new synthetic molecules. It is very computationally expensive to model every single atom in a molecule over even the shortest times (millionths of a second). This expense puts severe limits on the complexity of simulations that can be pursued. Dr. Shell and coworkers have developed an approach by which unnecessary atomic detail in simulations can be automatically identified. These unnecessary details are replaced by 'coarse-grained' models that require far fewer calculations. In turn, these coarse models permit simulations on dramatically larger scales. This capability opens new problems and systems of study. This project develops this basic approach by creating powerful ways to maintain high accuracy in highly coarse models and applies the new technique to understand peptide-based materials. This project provides educational opportunities for students at multiple levels, including involvement of those from underrepresented groups. Professor Shell mentors undergraduate researchers and participates in several campus-wide diversity initiatives that contribute to the professional development and research training programs at UCSB'sCalifornia Nanosystems Institute. The team develops strategies to improve the recruitment of women students in theoretical and computational research. A yearly seminar coordinated by Dr. Shell brings distinguished female researchers to campus to serve as role models for undergraduates, graduate students, and postdocs. While coarse-graining methods have been vigorously pursued in recent years, major practical and conceptual barriers remain that compromise coarse-grained (CG) model accuracy, transferability, and automation, and thus limit the general reliability of these all-important modeling approaches. This project leverages the relative entropy framework developed by the Shell group to create general new strategies for addressing these limitations. These new methods are rooted in rigorous statistical mechanical theory and state-of-the-art molecular simulation techniques. Specifically, the project creates robust strategies for efficiently and accurately modeling complex, multibody CG interactions across state conditions, chemistries, and systems, and for seamlessly including external constraints (like experimental information) in the bottom-up CG strategy. As an application of the techniques, this work develops a next-generation, general but sequence-sensitive CG peptide model suitable for understanding and predicting supramolecular self-assembly in emerging hybrid polymer-peptide materials.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.