CDS&E: Theoretical Models for Potential Energy Landscapes of Challenging Chemical Systems

大卫谢里尔是由化学理论，模型和计算方法计划在化学部和计算科学和数据支持的科学与工程计划的奖励支持，以开发计算方法，算法和软件研究非共价相互作用。 非共价相互作用是蛋白质折叠、药物对接、晶体包装和溶剂化的核心。 最近的实验提供了关于有机模型系统的详细数据，这些系统旨在分离和量化溶液中的单个非共价相互作用，但如果没有理论的帮助，它们仍然很难理解。 该项目旨在揭示影响这些实验有机系统中非共价相互作用的各种因素。Sherrill小组（1）使用密度拟合技术开发密度泛函理论（DFT）几何优化和频率分析的快速算法。(2)使用直接从蛋白质数据库（PDB）获取的测试案例，将可用的基准质量非共价相互作用能从几百扩展到几千。 这些数据对于验证和参数化非共价相互作用的理论模型至关重要。(3)识别耦合簇理论中的协同近似，以加速目标（2）中的计算，使用密度拟合，自然轨道和降阶技术的组合。(4)对CH/pi和pi-pi相互作用的实验模型复合物进行详细研究，以更好地了解这些相互作用，它们在溶液中如何运作，以及如何更有效地建模。Sherrill小组开发并使用计算方法来更好地了解分子之间的非键相互作用。 这种相互作用控制着药物如何找到它们的靶点以及分子晶体如何形成。 因此，本研究为合理药物设计和晶体工程的进展提供了有用的知识。 该项目提供了改进的理论和计算方法，通过（a）改进的计算机算法，以更快地计算相互作用，和（B）生成一个大型数据库的高质量的基准数据，可用于测试和改进新的理论模型的非键合接触。 基准数据将通过一个门户网站公布。 开发的软件将在开放源代码许可证下自由发布。 该项目不仅为学生提供如何使用分子模拟软件的培训，而且还提供如何编写分子模拟软件的培训。

David Sherrill is supported by an award from the Chemical Theory, Models and Computational Methods program in the Chemistry Division and the Computational Science and Data-enabled Science and Engineering Program to develop computational methods, algorithms and software for studying non-covalent interactions. Non-covalent interactions are central to protein folding, drug docking, crystal packing, and solvation. Recent experiments provide detailed data on organic model systems meant to isolate and quantify individual non-covalent interactions in solution, yet they remain hard to understand without the aid of theory. This project seeks to unravel the various factors influencing non-covalent interactions in these experimental organic systems. The Sherrill group is (1) Developing faster algorithms for density functional theory (DFT) geometry optimization and frequency analysis, using density fitting techniques.(2) Expanding the available set of benchmark-quality non-covalent interaction energies from a few hundred to several thousand, using test cases taken directly from the Protein Data Bank (PDB). This data is critical for validating and parameterizing theoretical models of non-covalent interactions.(3) Identifying synergistic approximations in coupled-cluster theory to accelerate the computations in Goal (2), using combinations of density-fitting, natural orbitals, and rank-reduction techniques.(4) Performing detailed studies of experimental model complexes of CH/pi and pi-pi interactions to better understand these interactions, how they operate in solution, and how they might be more effectively modeled.The Sherrill group develops and uses computational methods to better understand non-bonded interactions between molecules. Such interactions control how drugs find their targets and how molecular crystals form. Hence, this research provides knowledge useful for advances in rational drug design and crystal engineering. This project provides improved theoretical and computational methods for modeling such non-bonded interactions through (a) improved computer algorithms to compute interactions more quickly, and (b) generation of a large database of high-quality benchmark data that can be used to test and improve new theoretical models of non-bonded contacts. The benchmark data will be made publicly available through a web portal. The software developed will be freely released under an open-source license. This project provides training for students not only in how to use molecular modeling software, but also in how to write molecular modeling software.