以蛋白质色谱的科学发展和技术创新为目标，以多尺度界面分子行为的科学研究为主线，运用多维实验检测、量子化学/分子力学分析、分子对接和多尺度分子动力学模拟方法，进行系统的理论和实验研究。内容包括：在分子-分子界面解析蛋白质-亲和配基以及蛋白质自组装体（病毒样颗粒）中蛋白质分子间的相互作用；在分子-溶剂界面解析蛋白质-配基和蛋白质-蛋白质的结合作用及其溶液调控机制；在分子-固液界面解析蛋白质与表面配基的相互作用和蛋白质分子传递行为。籍此获得蛋白质的界面分子行为的完整科学描述和微观机理解析，建立亲和配基的仿生设计方法以及高效传质表面的理性设计方法，开发新型高效的蛋白质色谱分离技术，实现抗体和病毒样颗粒等重要蛋白质和蛋白质自组装体的高选择性、高柱效、高容量和高速度色谱分离纯化。该项目提出了从基础科学问题的解析到技术创新和应用的完整研究构想，对促进生物分离科学和技术的发展具有重要理论意义和应用价值。

Chromatography is the key technology in bioseparations. Taking the scientific development and technological innovation of adsorption chromatography as the objectives, this project is proposed to systematically study the multi-scale interfacial phenomena of protein chromatography. It will be carried out theoretically and experimentally by comprehensively using multiple experimentations and instrumental analyses, quantum chemistry/molecular mechanics analyses, molecular docking and multi-scale molecular dynamics simulations. More specifically, the molecular interactions between protein and its ligand as well as protein-protein in the self-assembly of proteins (e.g., virus-like particles, VLP) will be investigated at the molecular interfaces. The effects of solution environments on the affinity interactions will then be studied to find the regulation mechanisms of solution conditions. Finally, the affinity interactions and molecular transport phenomena at adsorbent surfaces with immobilized ligands will be extensively examined. Through the comprehensive studies, it is expected to acquire novel scientific insights into the interfacial phenomena of protein molecules and the micro-scale mechanisms of molecular transport at ligand surfaces. The new knowledge and findings would lead to the establishment of a biomimetic design methods for affinity ligands of proteins such as antibody, capsomere and VLP, as well as the ligand surfaces that could offer high-performance mass transport of bound proteins, resulting in the development of high-performance affinity chromatography of proteins for antibody and VLP. Hence, this project has proposed to realize technological innovation of protein chromatography via fundamental studies focusing on the multi-scale interfacial phenomena. The outcomes of the research would greatly contribute to the development of bioseparation science and technology.