亚浓聚合物溶液中蛋白扩散及反应动力学的介观统计理论研究

亚浓聚合物溶液通常被用于模拟细胞拥挤环境，研究该类复杂溶液中蛋白的扩散及反应动力学，揭示拥挤效应的影响，对深入理解细胞内生命过程等具有十分重要的意义。本项目拟发展介观统计方法，研究蛋白等生物大分子在亚浓聚合物溶液中的扩散及反应动力学。主要内容包括：（1）发展模耦合理论并结合广义郎之万方程，研究蛋白反常扩散动力学，揭示拥挤效应导致的动力学非均匀性，探索扩散系数对Stokes-Einstein关系偏离的机制；（2）发展动力学无序理论并结合瓶颈涨落模型，研究蛋白与配体结合反应动力学，揭示拥挤效应及蛋白构型涨落的重要影响；（3）结合上述两方面，进一步研究蛋白-蛋白结合反应动力学，建立扩散控制和反应控制模型下的结合速率与溶液浓度、粘度等的定量关系。本项目的研究将为深入理解复杂溶液中蛋白扩散及反应动力学相关实验提供理论支撑，为探索细胞等拥挤环境中药物输运、蛋白相互作用等复杂动力学过程提供新的研究方法。

Studying the dynamical behavior for macomolecules in crowding environments is critically important for deep understanding relevant intracellular life processes. We aim to develop a mesoscopic statistical modeling to systematically analyze the diffusive dynamics and reaction kinetics in complex solutions for biomolecules such as proteins. The Main contents include: (1) Based on generalized Langevin equation and mode coupling theory, we study the anomalous diffusive dynamics of proteins in semidilute polymer solutions. The dynamical heterogeneity associated to crowded effect as well as the deviation of diffusion coefficient from Stokes-Einstein relation will be comprehensively studied. (2) We will develop the dynamical disorder theory based on fluctuating bottleneck model for the protein-ligand binding kinetics . In particular, the influence of protein conformational fluctuation on the binding rate will be revealed. (3) Combining the anomalous diffusive dynamics and Kramers rate theory, we will establish an efficient theoretical framework to analyze the protein-protein association rate theory in semidilute polymer solutions. The quantitative relation between the association rate and the solution density and viscosity will be explicitly calculated. Our theoretical work will be applied to understand the experiments concerning protein diffusion and reaction in crowding environments. Our work will provide a novel and effective theoretical method to study the complex dynamical behavior in much more complicated celluar environments. Moreover, it will make also contribution to the development of the mesoscopic statistical mechanics for the study of complex systems.