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

用于表征构象柔性分子溶剂化壳中溶剂波动的增强采样方法

• 批准号: 1665339
• 负责人: Amish Patel
• 金额: $ 36万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1665339&HistoricalAwards=false
• 关键词: Enhanced; Sampling; Methods; Characterizing; Solvent

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.

宾夕法尼亚大学的阿米什·帕特尔（Amish Patel）获得了化学学部化学理论、模型和计算方法项目的奖励，他开发了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，如聚合物或多肽，在各种材料和生物环境中发挥着重要作用，从聚合物加工到药物输送。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两种以上不同的构象或分子形状。例如，在不利或不良的溶剂中，聚合物采用塌陷的球形形状，以尽量减少其原子与溶剂之间的接触，而在有利或良好的溶剂中，聚合物变得延伸。了解柔性溶质与其溶剂之间的相互作用是至关重要的，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，都受到它们的形状的强烈影响。Patel教授和他的同事开发了专门的模拟方法来表征柔性溶质和溶剂之间相互作用的强度，以了解这种相互作用如何依赖于溶质的特性、溶剂化环境和热力学条件。帕特尔教授还制作了教育电影，向K-12的学生和老师介绍不可思议的柔性分子世界。溶解在液体中的构象柔性溶质，如水中的聚合物或多肽，在各种材料和生物分子环境中起着重要作用，其中溶质的性质，以及它们的相互作用和组装，受到它们的分子构象的强烈影响。柔性分子可以存在于多种构象中，但通常表现为两个或多个由自由能垒分隔的稳定盆地；这些盆地以及它们之间的过渡不仅是由溶质固有的分子内相互作用决定的，而且是由多体溶质-溶剂相互作用决定的。通过改进采样方法来描述溶质-溶剂的集体相互作用，Patel教授和他的同事试图建立这样的相互作用是如何依赖于溶质的特性，它的溶剂化环境，以及随之而来的热力学条件的理解。最终，这种对柔性溶质的无溶剂化能量景观的理解可能为精确控制溶质构象转变铺平道路，对响应材料和药物传递载体的设计具有重要意义。

项目成果

Protein Hydration Thermodynamics: The Influence of Flexibility and Salt on Hydrophobin II Hydration

蛋白质水合热力学：柔韧性和盐对疏水蛋白 II 水合的影响

• DOI: 10.1021/acs.jpcb.7b12060
• 发表时间: 2017
• 期刊: The Journal of Physical Chemistry B
• 作者: Remsing, Richard C.;Xi, Erte;Patel, Amish J.
• 通讯作者: Patel, Amish J.

Protein Hydration Waters Are Susceptible to Unfavorable Perturbations

• DOI: 10.1021/jacs.8b11448
• 发表时间: 2019-02-06
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Rego, Nicholas B.;Xi, Erte;Patel, Amish J.
• 通讯作者: Patel, Amish J.

Characterizing the Interplay between Polymer Solvation and Conformation

• DOI: 10.1021/acs.jpcb.1c02191
• 发表时间: 2021-05-12
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Dhabal, Debdas;Jiang, Zhitong;Patel, Amish J.
• 通讯作者: Patel, Amish J.

Antifreeze protein hydration waters: Unstructured unless bound to ice

• DOI: 10.1073/pnas.1810812115
• 发表时间: 2018-08
• 期刊: Proceedings of the National Academy of Sciences
• 作者: Sean M. Marks;Amish J. Patel

Understanding Hydrophobic Effects: Insights from Water Density Fluctuations

了解疏水效应：水密度波动的见解

• DOI: 10.1146/annurev-conmatphys-040220-045516
• 发表时间: 2022
• 期刊: Annual Review of Condensed Matter Physics
• 影响因子: 22.6
• 作者: Rego, Nicholas B.;Patel, Amish J.
• 通讯作者: Patel, Amish J.