中文摘要：

4-巯乙基吡啶（MEP）是一种新型的疏水性电荷诱导层析（HCIC）配基,具有良好的抗体分离性能,采用分子模拟方法研究MEP配基与IgG间的分子相互作用,以探讨HCIC分离机制.先通过分子对接搜索IgG分子Fc片段A链的蛋白表面,确定12个可能与MEP结合的位点区域,然后用分子动力学模拟考察了其中6个位点的结合性能.结果表明,MEP在Fc-A链表面的结合具有疏水倾向性,pH中性条件下,MEP能稳定地结合在TYR319和LEU309附近的位点,并与两者形成氢键作用,该区域具有疏水性极强的口袋结构;其他位点的结合较不稳定,受MEP取向影响大.在pH4.0酸性条件下,原先稳定结合的MEP快速从Fc-A链表面脱离,主要原因是MEP和Fc间的静电排斥作用,以及疏水作用减弱和氢键结合的消失.通过分子模拟方法,从分子水平验证了HCIC独特的作用机理：疏水相互作用主导吸附,静电排斥作用协助解吸.

英文摘要：

Hydrophobic charge induction chromatography （HCIC） with 4-mercaptoethyl-pyridine （MEP） as the ligand has been proved to be effective for the separation of antibodies from different feedstocks. In the present work, the methods of molecular simulation are introduced to study the interactions between MEP and IgG. Firstly, molecular docking is used to identify the potential binding sites around the protein surface of Fc Chain A of IgG, and 12 potential binding sites are found. Then 6 sites are further studied using the molecular dynamics simulations. The results indicate that MEP ligand tends to bind on the hydrophobic area of Fc Chain A surface. At neutral conditions, MEP can bind stably on the site around TYR319 and LEU309 of Fc Chain A, which shows obviously a pocket structure with strong hydrophobicity. The analysis of trajectory reveals that hydrogen bonds exist between MEP and the former two amino acids around the simulation period. The binding of MEP to other sites are relatively unstable, and depends on the initial binding modes of MEP. When the pH lowers to 4.0, it can be found that MEP bound formerly on the Fc Chain A departs quickly due to the electrostatic repulsion, weaker hydrophobic interaction and the disappearance of hydrogen bonds. With the aids of molecular simulations, the separation mechanism of HCIC is verified from the view of molecular interactions-the binding with hydrophobic interactions at neutral condition and the desorptionwith electrostatic repulsion at acid condition.