Activated and nonlinear kinetics in biomolecules and interfaces

亚利桑那州立大学的Dimitry Matyushov获得了化学系化学理论、模型和计算方法项目的支持，用于蛋白质的理论和计算研究。 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。所有的生命能量都是通过质子中的电子穿过细胞膜来产生和储存的，这是由膜结合蛋白质执行的功能。同时，细胞体积的80%是水，其主要以其界面形式存在于膜的蛋白质和脂质周围。蛋白质和界面水，“生命的基质”，如何在他们的功能耦合在很大程度上仍然是一个谜，需要理论和实验研究。该项目所解决的一系列问题涉及生命能量效率、生理能量流以及非平衡分子系统产生的基本工作原理等最深层次的问题。 Matyushov教授和他的研究小组积极参与当地高中生参与的推广，研究和教育计划。这一理论项目与实验研究密切相关，它表明蛋白质从根本上说是非平衡系统，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的标准热力学温度。 在上一个供资周期进行的计算研究表明，蛋白质比水“热“三倍。这种观点的直接后果是反应活化屏障的强烈抑制。酶的催化作用在很大程度上是其非平衡状态的函数，该非平衡状态随着时间的推移而变化。死亡状态？由于构象动力学探索的配置空间的吉布斯分布。老化过程必须终止，酶在达到这种平衡状态之前重置。 该项目将氧化还原活性蛋白质的酶促效率与蛋白质-水界面结构和与活化屏障交叉相关的集体变量的玻璃化老化动力学联系起来。 该项目解决了以下实际问题：（a）氧化还原蛋白质的分解温度和与热浴平衡的动力学。(b)水界面磁化率的理论与模拟及其与本体水的区别。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、介电谱和蛋白质介电泳。(c)应用于界面测试的溶液非线性介电响应理论。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.