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Activated and nonlinear kinetics in biomolecules and interfaces

生物分子和界面中的活化和非线性动力学

基本信息

批准号：
1800243
负责人：
Dmitry Matyushov
金额：
$ 45.89万
依托单位：
Arizona State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-15 至 2022-03-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1800243&HistoricalAwards=false
关键词：
Activated nonlinear kinetics biomolecules interfaces

项目摘要

Dimitry Matyushov of Arizona State University is supported by an award from the Chemical Theory, Models and Computational Methods Program in the Division of Chemistry for theoretical and computational studies of proteins. Proteins provide the main building material of cells and multicellular organisms. In addition, protein enzymes are working horses of the cell catalyzing all chemical reactions required for life. All energy of life is produced and stored by moving electrons in protons across the cellular membrane, a function performed by membrane-bound proteins. At the same time, 80% of the cell's volume is water, which mostly exists in its interfacial form surrounding proteins and lipids of membranes. How proteins and interfacial water, the "matrix of life", couple in their function is still largely a mystery requiring both theoretical and experimental studies. The set of questions, addressed by this project, touches on the deepest problems of energy efficiency of life, its physiological energy flow, and the fundamental principles of work produced by non-equilibrium molecular systems. Professor Matyushov and his research group are actively engaged in an outreach, research and education program involving local high school students. This theoretical project, which is deeply connected to experimental studies, suggests that proteins are fundamentally non-equilibrium systems in which the time-scales of protein function are often shorter than the time-scales of equilibration achieved through conformational dynamics. This non-equilibrium nature of proteins requires two temperatures: the configurational temperature of the non-equilibrium protein and the standard thermodynamic temperature of the surrounding bath. Computational studies performed in the previous funding cycle have shown that proteins are up to three times "hotter"than water. A direct consequence of this perspective is a strong depression of the reaction activation barrier. The catalytic action of the enzyme is very much a function of its non-equilibrium state, which ages to the ?dead state? of the Gibbs distribution due to conformational dynamics exploring the configuration space. The aging process has to be terminated and the enzyme reset before this equilibrium state is reached. The project connects enzymatic efficiency of redox active proteins with the protein-water interfacial structure and glassy aging dynamics of collective variables linked to the activated barrier crossing. The project addresses the following practical questions: (a) Configurational temperature of redox proteins and the dynamics of equilibration with the thermal bath. (b) Theories and simulations of interfacial susceptibility of water and its distinction from water in the bulk. This problem connects to a number of experimental techniques such as depolarized light scattering, THz absorption, dielectric spectroscopy, and protein dielectrophoresis. (c) A theory of non-linear dielectric response of solutions applied to testing of interfaces. Collaborative initiatives as a part of the project aim at linking theory to experiment.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.

亚利桑那州立大学的Dimitry Matyushov获得了化学部化学理论、模型和计算方法计划颁发的蛋白质理论和计算研究奖。蛋白质是细胞和多细胞生物体的主要构建材料。此外，蛋白质酶是细胞的工作马，催化生命所需的所有化学反应。生命的所有能量都是通过在细胞膜上移动质子中的电子来产生和储存的，这一功能是由结合在细胞膜上的蛋白质完成的。同时，细胞体积的80%是水，水主要以界面形式存在于细胞膜的蛋白质和脂类周围。蛋白质和界面水--“生命的基质”--是如何结合在一起的，这在很大程度上仍然是一个谜，需要理论和实验两方面的研究。这组问题，由这个项目解决，涉及生命能量效率的最深层次问题，它的生理能量流动，以及非平衡分子系统产生功的基本原理。Matyushov教授和他的研究小组正在积极参与一项涉及当地高中生的外展、研究和教育项目。这个与实验研究密切相关的理论项目表明，蛋白质是基本的非平衡系统，其中蛋白质功能的时间尺度往往短于通过构象动力学实现平衡的时间尺度。蛋白质的这种非平衡性质需要两个温度：非平衡蛋白质的构型温度和周围浴液的标准热力学温度。在之前的资助周期中进行的计算研究表明，蛋白质的温度最高可达水的三倍。这一观点的一个直接后果是反应活化障碍的强烈抑制。酶的催化作用在很大程度上取决于它的非平衡态，即酶的非平衡态达到死态。由于构象动力学探索构型空间而导致的吉布斯分布。在达到这种平衡状态之前，必须终止老化过程并重新设置酶。该项目将氧化还原活性蛋白质的酶效率与蛋白质-水界面结构和与激活屏障跨越相关的集体变量的玻璃化老化动力学联系起来。该项目解决了下列实际问题：(A)氧化还原蛋白的构型温度和与热浴的平衡动力学。(B)水的界面磁化率的理论和模拟及其与整体水的区别。这个问题与许多实验技术有关，如去偏振光散射、太赫兹吸收、介电光谱学和蛋白质介电泳法。(C)适用于界面测试的溶液的非线性介电响应理论。作为项目的一部分，合作倡议旨在将理论与实验联系起来。这一奖项反映了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。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Interfacial structural crossover and hydration thermodynamics of charged C 60 in water

带电C 60 在水中的界面结构交换和水化热力学

DOI：
10.1039/c8cp05422c
发表时间：
2018
期刊：
Physical Chemistry Chemical Physics
影响因子：
3.3
作者：
Sarhangi, Setare Mostajabi;Waskasi, Morteza M.;Hashemianzadeh, Seyed Majid;Matyushov, Dmitry V.
通讯作者：
Matyushov, Dmitry V.

Dipolar susceptibility of protein hydration shells

蛋白质水化壳的偶极敏感性