基于荷电粒子和聚电解质促进同电荷蛋白质复性作用的发现和表面静电排斥作用对抑制蛋白质聚集作用的认识，提出了静电排斥表面调控蛋白质复性的分子机理及其应用的研究构想。首先系统研究荷电粒子和聚电解质结构对蛋白质复性的影响规律，建立蛋白质在荷电粒子表面和聚电解质溶液等静电排斥纳米空间中的静电相互作用模型，研究蛋白质分子结构参数对静电相互作用和分子表面方位动态行为的影响；同时，利用多尺度分子动力学模拟研究蛋白质在静电排斥表面的构象转换和自相互作用，阐释静电排斥表面调控蛋白质复性的分子机理；在此基础上，设计合成新型结构的荷电粒子，研究荷电表面结构对蛋白质复性的影响，优化荷电介质性能参数；最后研究建立离子交换色谱辅助同电荷蛋白质复性和纯化方法，优化同电荷柱色谱复性过程，实现同电荷介质促进包含体蛋白质复性和纯化。本研究将发展蛋白质复性理论，创新蛋白质复性方法，具有重要理论研究意义和应用前景。

On the basis of our findings that protein refolding could be greatly facilitated by like-charged ion-exchangers and polyelectrolytes, as well as the understanding of the contributions of electrostatic repulsion of charged surfaces that induce oriented protein alignments that result in protein aggregating suppression, this project is proposed to study the molecular mechanisms of protein refolding modulated by the electrostatically repulsive charged surfaces as well as in the vicinity of polyelectrolytes. First of all, protein refolding in the presence of various charged particles and polyelectrolytes will be investigated to reveal the influences of important charge parameters on protein refolding and aggregation. Then, electrostatic interaction models for the folding protein in the electrostatically repulsive surfaces of charged particles and polyelectrolyte solutions will be established to examine the effects of protein structural parameters on the dynamics of electrostatic interaction energy, surface distance and orientation of protein molecules. At the same time, multi-scale molecular dynamics simulations will be carried out to study the conformational transition and intermolecular interactions of folding proteins in the electrostatically repulsive surfaces. The comprehensive researches will lead to the understanding of the molecular mechanisms of protein refolding modulated by the electrostatically repulsive surfaces. Based on the theoretical outcomes, novel charged media will be designed and synthesized for facilitating protein refolding, leading to the optimized medium structures in pore size, pore-size distribution, charged group chemistry and charge density. Finally, refolding and purification of like-charged proteins on ion-exchange column chromatography will be established and optimized to realize inclusion body protein refolding and purification. It is expected that the outcomes of this project will greatly contribute to the theoretical development of protein refolding, and lead to the invention of novel protein refolding technology. Therefore, this project is of theoretical importance and has great potential in protein refolding applications.