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

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

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.