This award by the Experimental Physical Chemistry Program supports the collaborative efforts of Pablo G. Debenedetti (Princeton University),C. Austen Angell (Arizona State University), Peter Rossky (University of Texas at Austin), and H. Eugene Stanley (Boston University) in understanding cooperative phenomena in water and aqueous solutions. This project will investigate how solvent organization and structure affects cooperative processes occurring over microscopic (e.g., protein folding), mesoscopic (e.g., fibrilization), or macroscopic (e.g., phase transitions) length scales, and explore whether there exist common features or principles across a broad range of these cooperative transitions. This interdisciplinary collaboration will include a novel experimental approach to study the energetics and kinetics of protein folding (and other ordering phenomena) using non-crystallizing but non-perturbing solvents; computer simulations of phase transitions in two-scale spherically-symmetric model systems that exhibit water-like dynamics and solvation thermodynamics; theoretical and computational investigations of protein phase diagrams and directed evolution using water-explicit lattice models; and computational studies of the emergence of molecular mobility upon hydration of protein powders.
An improved understanding of the role of water and co-solutes on cooperative processes and molecular order has far-reaching consequences for directed self-assembly of advanced materials and the molecular basis of life processes, including metabolic control of gene expression, protein folding (and misfolding in disease states) and the long-term preservation and storage of natural tissues and materials. The proposed work will also provide outstanding opportunities for undergraduates, graduate students, and postdoctoral researchers to integrate experiment and theory and work in a team at the interface of chemistry and biology.
The goal of this project has been to understand so-called cooperative phenomena in water, aqueous solutions and water-biomolecule systems. Cooperative processes involve the sudden and concerted participation of a large number of basic units: amino acid residues in protein folding, proteins in fibrilization, small molecules in first-order phase transitions, or complex molecules in self-assembly. The main outcomes of this project are listed below. (1) By trapping proteins in non-crystalline solid matrices, we developed an experimental technique that allows protein folding to be followed spectroscopically on arbitrarily long time scales. This result is relevant to the basic science of protein folding and to the rational design of therapeutic formulations in the pharmaceutical industry. (2) When two macroscopic and repulsive surfaces are immersed in water, evaporation of the confined liquid is favored thermodynamically below a critical separation: the evaporation length scale. We evaluated the evaporation length scale of water, and compared it to that of several common organic liquids over a broad range of temperatures, at atmospheric pressure. We showed that water’s evaporation length scale is of the order of 1 micron, appreciably larger than generally thought; that the evaporation length scale of several common organic liquids, although systematically smaller than water’s, is likewise macroscopic, attesting to the generality of the phenomenon; and that the only physical property that causes water’s evaporation length scale to be larger than that of other liquids is its surface tension. These results are relevant to the design of self- cleaning surfaces and anti-ice coatings. (3) Using advanced molecular simulation techniques, we showed that a widely-used model of water separates into two liquid phases at low temperatures. This result is relevant to the behavior of water in the atmosphere, where it can exist as a so-called supercooled liquid below its equilibrium freezing point. (4) We used advanced molecular simulation methods to compute accurately, for the first time, the solubility of long-chain hydrocarbons in water. This result is important in environmental and water management applications. (5) Molecules that can exist as two non-superimposable mirror images, like our hands, are said to be chiral. Chirality is an essential characteristic of life as we know it: biological molecules are composed of simple units that exhibit one of the two possible chiral forms. Using simple models with microscopic degrees of freedom, we demonstrated plausible mechanisms whereby a spontaneous chiral preference can arise under conditions that may be relevant to the early prebiotic earth. (6) Using path-sampling molecular simulation methods, we calculated the rates and elucidated the mechanism by which water evaporates when it is confined by hydrophobic surfaces in nanometer-sized cavities. This phenomenon, known as capillary evaporation, is believed to be important in protein folding, the binding of small molecules to proteins, and the opening and closing of ion channels. We showed that the evaporation process occurs through the formation of tube-like cavities. Our calculations provide detailed information on the rate at which hydrophobic cavities in proteins are emptied, as a function of cavity size and temperature.
