Theoretical Models for Potential Energy Landscapes of Challenging Chemical Systems

佐治亚理工大学的David Sherrill得到了化学理论、模型和计算方法项目的支持，该项目开发理论和计算方法来研究分子之间弱的、非键的相互作用。这种相互作用决定了药物如何与体内的靶标结合，分子如何填充到固体中，以及液体的行为。因此，分子之间的相互作用对科学和技术至关重要，更好地了解这些相互作用有助于设计更好的材料或更有效的药物。谢里尔和他的研究小组专注于基于量子力学的新理论技术。他们用用户友好的、开源的、广泛可用的和免费的计算机软件来实施他们的方法。这使得其他研究人员能够在更多情况下更准确地建模和分析分子之间的相互作用，并提供更高级别的细节。该项目有助于对博士后、研究生和本科生进行量子化学方法和软件开发方面的培训。该项目是由高级网络基础设施司的计算和数据使能科学与工程计划共同创立的。对称适应微扰理论(SAPT)将被扩展到计算不同分子片段之间的相互作用，即使这些片段在同一分子中(这在当前版本的SAPT中是不可能的)。分子内SAPT允许研究分子扭转平衡中的连接基如何影响它们所要研究的相互作用。这些技术还被扩展到具有未配对电子的分子，从而能够研究蛋氨酸-芳香族接触如何有助于蛋白质稳定，以及这些接触如何在蛋氨酸基团电离后改变其强度。该项目还在研究用于扩展系统的高精度计算的各种多体展开近似(包括密度嵌入)。作为该项目的一部分开发的方法正在作为开放源码软件实施，以供整个科学界使用。分子间相互作用模型能力的增强应该会使化学、材料科学、生物化学和药物设计方面的研究人员受益。与此同时，正在开发相关的计算实验室练习，教授分子间相互作用的基本概念。

David Sherrill of Georgia Tech University is supported by an award from the Chemical Theory, Models and Computational Methods program to develop theoretical and computational approaches to study weak, non-bonded interactions between molecules. Such interactions determine how medicines bind to their targets in the body, how molecules pack into solids, and how liquids behave. Hence, interactions between molecules are of fundamental importance for science and technology, and understanding these interactions better could aid in the design of better materials or more effective medicines. Sherrill and his research group focus on new theoretical techniques based on quantum mechanics. They implement their methods in user-friendly, open-source, widely-available and free computer software. This allows other researchers to model and analyze interactions between molecules more accurately, in more situations, and with a higher level of detail. The project is contributing to the training of postdocs, graduate students, and undergraduates in quantum chemistry methods and software development. The project is cofounded by the Computational and Data-enabled Science and Engineering Program in the Division of Advanced Cyberinfrastructure. Symmetry-adapted perturbation theory (SAPT) will be extended to compute interactions between different molecular fragments, even when those fragments are in the same molecule (this is not possible with current versions of SAPT). The intramolecular SAPT allows investigations of how linker groups in molecular torsion balances affect the interactions they have been made to study. These techniques are also being extended to molecules with unpaired electrons, allowing an investigation of how methionine-aromatic contacts contribute to protein stabilization, and how these contacts change their strength upon ionization of the methionine group. The project is also investigating various many-body expansion approximations (including density embedding) for use in high-accuracy computations of extended systems. The methods developed as part of this project are being implemented as open-source software, to be made available to the entire scientific community. The enhanced ability to model interactions between molecules should benefit researchers in chemistry, materials science, biochemistry, and drug design. At the same time, associated computational laboratory exercises are being developed that teach fundamental concepts of intermolecular interactions.