Enhanced Sampling Methods for Characterizing Solvent Fluctuations in the Solvation Shells of Conformationally Flexible Molecules

宾夕法尼亚大学的Amish Patel获得了化学系化学理论，模型和计算方法计划的奖项，以开发用于研究柔性分子与溶解它们的液体之间相互作用的计算方法。柔性分子，如聚合物或肽，在从聚合物加工到药物递送的各种材料和生物环境中发挥重要作用。根据这些分子与周围溶剂之间的相互作用是否有利，柔性溶质可以采用两种或更多种不同的构象或分子形状。例如，在不利的或不良的溶剂中，聚合物采用塌陷的球形形状以使其原子与溶剂之间的接触最小化，而在有利的或良好的溶剂中，聚合物变得延伸。了解柔性溶质与其溶剂之间的相互作用至关重要，因为柔性溶质的机械，光学和其他性质，它们与其他分子的相互作用以及它们按预期发挥作用的能力受到其形状的强烈影响。Patel教授和他的同事开发了专门的模拟方法，用于表征柔性溶质和溶剂之间的相互作用强度，以了解这种相互作用如何取决于溶质的特性，溶剂化环境和热力学条件。Patel教授还制作了教育电影，向K-12学生和教师介绍了令人难以置信的柔性分子世界。溶解在液体中的构象柔性溶质，如水中的聚合物或肽，在各种材料和生物分子环境中发挥着重要作用，其中溶质的性质，以及它们的相互作用和组装，受到分子构象的强烈影响。柔性分子可以存在于多种构象中，但通常显示两个或更多个由自由能垒隔开的稳定盆地;这些盆地以及它们之间的转变不仅由溶质的固有分子内相互作用决定，而且还由多体溶质-溶剂相互作用决定。通过开发用于表征这种集体溶质-溶剂相互作用的增强型采样方法，Patel教授和他的同事试图建立对这种相互作用如何取决于溶质的特性，其溶剂化环境以及随之而来的热力学条件的理解。最终，这种理解的溶剂化自由充满活力的景观灵活的溶质可以铺平道路，精确控制溶质的构象转变，具有重要意义的设计响应材料和药物输送载体。

Amish Patel of the University of Pennsylvania is supported by an award from the Chemical Theory, Models and Computational Methods Program in the Chemistry Division to develop computational methods for studying the interactions between flexible molecules and the liquids in which they are dissolved. Flexible molecules, such as polymers or peptides, play an important role in diverse materials and biological contexts, ranging from polymer processing to drug delivery. Depending on whether the interactions between such molecules and the surrounding solvent are favorable, flexible solutes can adopt two or more distinct conformations or molecular shapes. For example, in an unfavorable or poor solvent, polymers adopt a collapsed globular shape to minimize contact between their atoms and the solvent, whereas in a favorable or good solvent, polymers become extended. Understanding the interactions between flexible solutes and their solvent is crucial because the mechanical, optical and other properties of flexible solutes, their interactions with other molecules, as well as their ability to function as expected, are strongly influenced by their shapes. Professor Patel and his coworkers develop specialized simulation methods for characterizing the strength of interactions between flexible solutes and the solvent to understand how such interactions depend on the characteristics of the solute, its solvation environment, and on thermodynamic conditions. Prof. Patel also creates educational movies to introduce K-12 students and teachers to the incredible world of flexible molecules.Conformationally flexible solutes dissolved in liquids, such as polymers or peptides in water, play an important role in diverse materials and biomolecular contexts, wherein the properties of the solutes, as well as their interactions and assemblies, are strongly influenced by their molecular conformation. Flexible molecules can exist in a multitude of conformations, but often display two or more stable basins separated by free energetic barriers; these basins as well as the transitions between them are determined, not only by the inherent intra-molecular interactions of the solute, but also by the many-body solute-solvent interactions. Through the development of enhanced sampling methods for characterizing such collective solute-solvent interactions, Professor Patel and his coworkers seek to establish an understanding of how such interactions depend on the characteristics of a solute, its solvation environment, and the attendant thermodynamic conditions. Ultimately, such an understanding of the solvation free energetic landscape of flexible solutes may pave the way for precisely controlling solute conformational transitions, with important implications on the design of responsive materials and drug delivery vectors.