Theoretical methods in chemistry and biophysics

点击翻译按钮获取中文摘要

Frank Brown of the University of California at Santa Barbara is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry to develop theoretical and computational tools for modeling cell membranes and enzymes. The Molecular Biophysics Cluster of the Division of Cellular and Molecular Biosciences also contributes to this award. Both membranes and enzymes are essential to biological function in the cells throughout the body. Membranes protect cells from their environment, provide a means to compartmentalize subcellular function, and act as a versatile scaffold for biochemical reactions involving membrane-associated proteins. Enzymes are biological catalysts that serve to accelerate chemical reactions and the metabolic processes dependent on these chemical reactions, thus making life possible. Professor Brown is studying the fundamental physics and chemistry underlying these biological systems using new mathematical and computational models to assist in the interpretation and understanding of the experimental measurements. This research serves the broad scientific community (chemistry, biochemistry, biophysics, biology, materials science and biomedicine) that relies upon the interpretation these experiments and advances understanding of human health. The work is having a further impact through the training of the next generation of scientists and the free distribution of software modules for simulation and analysis. The research is integrated with outreach and training through Professor Brown's ongoing involvement in the UC Chemistry Outreach and From Soccer to Science programs for grade-school children and their parents. Professor Brown also organizes conferences on biophysical dynamics and scientific simulation to widely disseminate his research results.The investigators are developing theoretical models, numerical tools and simulation algorithms for the study of lipid bilayer mechanics and dynamics and enzyme kinetics. Techniques to extract membrane viscosity from equilibrium molecular simulations are being developed. The interfacial regularized stokeslets methodology is being extended to allow calculation of the full hydrodynamic mobility matrix for membrane proteins. An algorithm to implicitly capture the hydrodynamic effects of water surrounding membranes in molecular simulations is being formulated. Continuum models for membrane structure and thermodynamics at two different levels of resolution are being refined and a general theoretical framework for modeling enzyme kinetics is being extended to allow the study of fluctuations about the mean (bulk) behavior. Several problems at the interface between chemistry and biophysics are being studied using these newly-developed tools. These applications include: lateral diffusion in protein-laden membranes; understanding and reconciling membrane bending moduli as measured via different experimental techniques; and single-molecule enzymology and the relation of lipid orientation fluctuations to Nuclear Magnetic Resonance (NMR) order parameters and neutron scattering measurements. In addition to training of the next generation of scientists on state-of-the-art analytic modeling and simulation techniques, the research is contributing to advanced software that is being disseminated as open-source modules for CHARMM and VMD, to help researchers bridge the gap between the fine-grained predictions of atomistic modeling and experimental observables. The project is integrated with outreach to grade-school students and their parents, to inspire the pursuit of careers in STEM and aspirations to college-level study, and with the organization of conferences on scientific simulation and biophysical dynamics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.