CAREER: Self-Assembly Through Water-Mediated Interactions: A New Statistical Thermodynamics and Simulations Approach

Rensselaer Polytechnic Institute, Troy NY

Investigators

Abstract

Abstract CTS-0134255 Garde, Shekhar Rensselaer Polytechnic Institute The goal of the CAREER proposal is to develop a successful research program for quantitative molecular modeling of biomolecular self-assembly processes in solution using fundamental understanding of the underlying water-mediated interactions. It presents a vision for combing statistical mechanical theories with novel efficient molecular simulation techniques to develop a generalized approach to study thermodynamic, structural, and kinetic aspects of biomolecular interactions. Quantitative modeling of biomolecules in solution, in general, and proteins in particular is of interest to chemical engineers because of its direct relevance to biotech and pharmaceutical applications, designing novel self-assembling materials, and applications in molecular medicine. This project focuses specifically on the T, P, and salt and cosolvent effects on protein stability and interactions in solution. To this end, the specific steps in the proposed research are: 1. (a) To quantify, using atomically detailed simulations and theory, interactions between various "archetype" (building blocks or protein constituents) solutes mediated by water. (b) To develop, for the first time, an extensive library of the distance dependent free energies of solute-solute interactions in water- the potentials of mean force (PMFs) - for archetype solutes as a function of temperature, pressure, and salt and cosolvent concentration. 2. To develop a general and highly efficient statistical mechanical approach that integrates water-mediated interactions contained in the PMF-library for applications to a variety of self-assembly processes in water. 3. To apply this predictive approach to study of protein thermodynamics as a function of various environmental stresses. Perform complementary large-scale explicit water simulations for selected test systems for investigation of further mechanistic details, assessment of predictions, and fine-tuning.