Theoretical methods in chemistry and biophysics

化学和生物物理学的理论方法

• 批准号: 1800352
• 负责人: Frank Brown
• 金额: $ 56.1万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1800352&HistoricalAwards=false
• 关键词: Theoretical; methods; chemistry; biophysics

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.

位于圣巴巴拉的加州大学的Frank Brown获得了化学系化学理论、模型和计算方法项目的奖项，以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学集群也有助于这个奖项。细胞膜和酶都是身体细胞生物功能的关键。 膜保护细胞免受其环境的影响，提供了一种划分亚细胞功能的方法，并作为涉及膜相关蛋白的生化反应的通用支架。 酶是生物催化剂，用于加速化学反应和依赖于这些化学反应的代谢过程，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础物理和化学，使用新的数学和计算模型来帮助解释和理解实验测量。 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模拟和分析软件模块，这项工作正在产生进一步的影响。 这项研究是通过布朗教授的持续参与加州大学化学外展和从足球到科学计划的小学生和他们的父母的推广和培训相结合。 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。研究人员正在为脂质双层力学和动力学以及酶动力学的研究开发理论模型、数值工具和模拟算法。 正在开发从平衡分子模拟中提取膜粘度的技术。 界面正则化stokeslets方法正在扩展到允许计算膜蛋白的完整流体动力学迁移率矩阵。 一个算法，以隐式捕捉水分子模拟膜周围的水动力学效应正在制定。 连续模型的膜结构和热力学在两个不同层次的分辨率正在完善和酶动力学建模的一般理论框架正在扩展到允许波动的平均（散装）行为的研究。 化学和生物物理学之间的接口的几个问题正在使用这些新开发的工具进行研究。 这些应用包括：在蛋白质负载膜的横向扩散;理解和协调膜弯曲模量通过不同的实验技术测量;和单分子酶学和脂质取向波动的关系，核磁共振（NMR）顺序参数和中子散射测量。 除了对下一代科学家进行最先进的分析建模和模拟技术的培训外，这项研究还有助于开发先进的软件，这些软件作为CHARMM和VMD的开源模块进行传播，以帮助研究人员弥合原子模型和实验观测值的细粒度预测之间的差距。 该项目与面向小学生及其家长的外联活动相结合，以激发对STEM职业的追求和对大学水平学习的渴望，并与科学模拟和生物物理动力学会议的组织相结合。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

项目成果

Dynamic correlations in lipid bilayer membranes over finite time intervals

有限时间间隔内脂质双层膜的动态相关性

• DOI: 10.1063/5.0129130
• 发表时间: 2023
• 期刊: The Journal of Chemical Physics
• 作者: Schoch, Rafael L.;Haran, Gilad;Brown, Frank L.
• 通讯作者: Brown, Frank L.

Motion of objects embedded in lipid bilayer membranes: Advection and effective viscosity

• DOI: 10.1063/1.5121418
• 发表时间: 2019-09-28
• 期刊: JOURNAL OF CHEMICAL PHYSICS
• 影响因子: 4.4
• 作者: Camley, Brian A.;Brown, Frank L. H.
• 通讯作者: Brown, Frank L. H.

Integrated rate laws for processive and distributive enzymatic turnover

进行性和分配性酶周转率的综合速率定律

• DOI: 10.1063/1.5097576
• 发表时间: 2019
• 期刊: The Journal of Chemical Physics
• 作者: Barel, Itay;Reich, Norbert O.;Brown, Frank L. H.
• 通讯作者: Brown, Frank L. H.

Pressure Unfolding of Proteins: New Insights into the Role of Bound Water

• DOI: 10.1021/acs.jpcb.1c04398
• 发表时间: 2021-07-26
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Arsiccio, Andrea;Shea, Joan-Emma
• 通讯作者: Shea, Joan-Emma