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，以开发蛋白质迁移率、电弹性和电导率的理论模型。 电子通过生物呼吸能量链和细菌光合作用中的蛋白质移动，以储存生物功能所需的能量。 加速这种电荷传输对于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输仍然令人困惑。Matyushov和他的研究小组将进行高性能计算机模拟和建模，以了解蛋白质中电荷传输的高效率。这一领域的一个新的和令人惊讶的发展是认识到蛋白质也是高效率的导体，尽管长期以来这些材料被认为是绝缘体。这种性质提供了生物保护免受氧化损伤，但也打开了大门，通过蛋白质电导率的变化，生物活性的单分子监测的新技术。Matyushov和实验同事将继续研究单分子连接中蛋白质导电机制的理论模型。 他还将开发通过介电泳从溶液中分离蛋白质的模型。他的团队最近开发的一种新理论预测了溶液中蛋白质对电场梯度的高灵敏度，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，以计算蛋白质的电导率及其对微流体设备中电场的敏感性。理论成果将通过面向工程师和生物化学家的广泛受众的书籍和评论文章传播。 拟议的工作是开发正式的理论和计算算法，以解决一般问题的非平衡（非遍历）采样蛋白质，并建立直接的联系，实验室实验。主要研究目标如下：（1）蛋白质中的非遍历采样和涨落耗散关系破坏的分析理论将解决从慢介质到快介质的矢量电荷输运问题以及蛋白质中电荷涨落对蛋白质氧化还原反应的影响。(2)蛋白质的平移和旋转扩散的理论将在竞争力产生随机平移和旋转方面发展。我们目前开发蛋白质介电电泳模型的努力将扩展到建立在纳米孔处捕获蛋白质的实用方法。(3)蛋白质单分子导电性理论的发展基于蛋白质内电荷载流子对构型空间的非遍历采样的思想。(4)蛋白质粘电弹性理论将在频率依赖的粘弹性模量和可电离的表面残基的溶剂化方面发展。该理论将提供记忆功能来描述蛋白质扩散率的复杂动力学，并建立一个通用框架，用于解决负责蛋白质流动性的力的非平衡波动。将拟议的活动与实验紧密联系起来，将有助于研究生和博士后研究员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。

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.