Transport Coefficients, Electroelasticity, and Conductivity of Proteins

亚利桑那州立大学的Dmitry Matyushov获得了化学系化学理论、模型和计算方法项目的奖励，他开发了蛋白质的迁移率、电弹性和电导率的理论模型。电子在生物呼吸能量链和细菌光合作用中通过蛋白质移动，为生物功能储存能量。加速这种电荷传输对生物性能和效率至关重要。蛋白质如何实现足够快的电子传递仍然是一个谜。Matyushov和他的研究小组将进行高性能的计算机模拟和建模，以加深对蛋白质中高效率电荷传输的理解。尽管长期以来人们认为蛋白质是绝缘体，但这一领域的一个令人惊讶的新发展是认识到蛋白质也是高效导体。这种特性提供了免受氧化损伤的生物保护，但也为通过改变蛋白质电导率来监测生物活性的单分子新技术打开了大门。Matyushov和他的实验同事将对单分子连接中蛋白质传导机制进行理论建模。他还将开发通过介质电泳从溶液中分离蛋白质的模型。他的团队最近发展了一种新理论，预测溶液中的蛋白质对电场梯度的高度敏感性，这为制药和生物医学应用中的蛋白质分离提供了新技术。这项工作的结果将以预测计算算法的形式提供给社区，以计算微流体装置中蛋白质的电导率及其对电场的敏感性。理论结果将通过书籍和评论文章传播给工程师和生物化学家的广泛受众。提出的工作是发展形式理论和计算算法，以解决蛋白质中非平衡（非遍历）采样的一般问题，并建立与实验室实验的直接联系。研究目标如下：(1)蛋白质中非遍数采样和涨落耗散关系的分析理论将解决从慢速介质到快速介质的矢量电荷传输问题以及蛋白质中电荷波动对蛋白质氧化还原反应的影响。(2)蛋白质的平动和旋转扩散理论将在产生随机平动和旋转的竞争力方面得到发展。我们目前开发的蛋白质电泳模型将扩展到建立在纳米孔捕获蛋白质的实用方法。(3)基于蛋白内电荷载体构型空间非遍历采样思想的蛋白质单分子电导率理论的发展。(4)根据频率依赖的粘弹性模量和可电离表面残基的溶剂化，将发展蛋白质粘电弹性理论。该理论将提供记忆功能来描述蛋白质扩散的复杂动力学，并为解决导致蛋白质迁移的力的非平衡波动建立一个一般框架。建议的活动与实验紧密联系将有助于研究生和博士后获得更广泛的学科视野，并学习合作研究的文化。该奖项反映了美国国家科学基金会的法定使命，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。

Dmitry Matyushov of Arizona State University is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry to develop theoretical models of Mobility, Electroelasticity, and Conductivity of proteins. Electrons move through proteins in biological respiratory energy chains and in bacterial photosynthesis to store energy for biological function. Speeding up this charge transport is critical for biological performance and efficiency. How proteins achieve sufficiently fast electron transport is still puzzling. Matyushov and his research group will perform high performance computer simulations and modeling to develop understanding of high efficiency of charge transport in proteins. A new and surprising development in this field is the realization that proteins are also high-efficiency conductors, despite long-held view of these materials as insulators. This property provides biological protection from oxidative damage, but also opens the door to new technologies of single-molecule monitoring of biological activity through changes in protein conductivity. Matyushov with experimental colleagues will pursue theoretical modeling of mechanisms of protein conductivity in single-molecule junctions. He will also develop models of separation of proteins from solutions by means of dielectrophoresis. A new theory recently developed in his group predicts high sensitivity of proteins in solution to electric field gradients, which offers new technologies for protein separation in pharmaceutical and biomedical applications. The results of this work will be available to the community in the form of predictive computational algorithms to calculate conductivity of proteins and their sensitivity to the electric field in microfluidic devices. Theoretical results will be disseminated through books and review articles targeting broad audience of engineers and biochemists. The proposed work is to develop formal theories and computational algorithms to address the general problem of nonequilibrium (nonergodic) sampling in proteins and to establish direct links to laboratory experiments. The following research goals will be pursued: (1) Analytical theories of nonergodic sampling and violation of fluctuation-dissipation relations in proteins will address the problem of vectorial charge transport from a slow to a fast medium and the effect of charge fluctuations in proteins on protein redox reactions. (2) Theories of protein translational and rotational diffusivity will be developed in terms of competing forces producing stochastic translations and rotations. Our current effort to develop models of protein dielectrophoresis will be extended to establish practical approaches to capture proteins at nanopores. (3) The development of a theory of single-molecule conductivity of proteins based on the idea of nonergodic sampling of the configuration space by intraprotein charge carriers. (4) A theory of protein viscoelectroelasticity will be developed in terms of frequency-dependent viscoelastic moduli and solvation of ionizable surface residues. The theory will provide memory functions to describe complex dynamics of protein diffusivity and to build a general framework for addressing nonequilibrium fluctuations of forces responsible for protein mobility. Strong connection of the proposed activities to experiment will help graduate students and postdoctoral fellows to gain a broader view of the discipline and learn the culture of collaborative research.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.