Theoretical methods in chemistry and biophysics

加州大学圣巴巴拉分校的Frank Brown获得了化学部化学理论、模型和计算方法项目的支持，该项目开发用于模拟细胞膜和酶的理论和计算工具。细胞和分子生物科学部的分子生物物理组也为这一奖项做出了贡献。膜和酶对人体细胞的生物功能都是必不可少的。膜保护细胞不受环境的影响，提供了一种划分亚细胞功能的方法，并充当了涉及膜相关蛋白的生化反应的多功能支架。酶是生物催化剂，可以加速化学反应和依赖于这些化学反应的新陈代谢过程，从而使生命成为可能。布朗教授正在研究这些生物系统的基本物理和化学基础，使用新的数学和计算模型来帮助解释和理解实验测量结果。这项研究服务于广泛的科学界(化学、生物化学、生物物理学、生物学、材料科学和生物医学)，这些科学界依赖于对这些实验的解释并促进对人类健康的理解。通过培训下一代科学家和免费分发用于模拟和分析的软件模块，这项工作正在产生进一步的影响。这项研究与外展和培训相结合，通过布朗教授持续参与加州大学化学外展和从足球到科学的计划，为小学生和他们的家长。布朗教授还组织生物物理动力学和科学模拟会议，广泛传播他的研究成果。研究人员正在开发用于研究脂质双层力学和动力学以及酶动力学的理论模型、数值工具和模拟算法。从平衡分子模拟中提取膜粘度的技术正在开发中。界面规则化的斯托克斯莱斯方法正在扩展，以允许计算膜蛋白的完整流体动力学迁移率矩阵。一种在分子模拟中隐含地捕捉膜周围水的流体动力学效应的算法正在形成中。膜结构和热力学在两个不同分辨率水平下的连续模型正在改进，模拟酶动力学的一般理论框架正在扩展，以允许研究平均(整体)行为的波动。使用这些新开发的工具，正在研究化学和生物物理之间的几个问题。这些应用包括：蛋白质膜中的侧向扩散；通过不同的实验技术测量的膜弯曲模数的理解和协调；单分子酶学以及脂质取向波动与核磁共振序参数和中子散射测量的关系。除了就最先进的分析建模和模拟技术对下一代科学家进行培训外，这项研究还为先进的软件做出了贡献，这些软件正在作为CHARMM和VMD的开源模块分发，以帮助研究人员弥合原子建模的细粒度预测和实验观测之间的差距。该项目与对小学生及其家长的推广活动相结合，以激励对STEM职业的追求和对大学水平研究的渴望，并与组织关于科学模拟和生物物理动力学的会议相结合。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.