Abstract: The molecular interaction between protein and surfactant and its implication on the refolding of the protein in vitro was investigated by using the simple lattice model with dynamic Monte Carlo simulation and canonical ensemble.The thermodynamic feasible status of the model protein, as described by HP model, and its folding intermediates were captured. Some of the folding intermediates were trapped into local energy minimum and could not proceed refolding into the native form. The addition of surfactant enriched both the species and the amount of folding intermediates by the way of forming protein-surfactant complex. The surfactant of weak hydrophobicity had little impact on the thermodynamic status of the protein but was effective in moving the folding intermediates out of local minimum energy entrapment, leading to a considerable increase in the refolding. On the other hand, the surfactant with strong hydrophobicity might block the folding process by forming stable protein-surfactant complex. In this case, the dissociation of the complex by stripping the surfactant was necessary so as to precede the folding process. The synergy of surfactant and denaturing environment for protein refolding was also confirmed. The simulation agreed well with prior experiment results in literature. This indicated the potential of using molecular simulation to explore the details of refolding process and to assist the design of suitable surfactant-like folding aids.

Key words: 分子模拟, HP模型, 表面活性剂, 折叠中间态, 动态Monte Carlo模拟, 蛋白质体外折叠

摘要： 采用分子模拟方法考察表面活性剂与蛋白质分子之间的相互作用及其对蛋白质折叠过程热力学特性的影响，蛋白质分子构建采用HP模型并引入了方阱类势函数.模拟结果显示：模型蛋白分子的某些折叠中间态会陷入局部能量最低状态而无法完成折叠;弱疏水性表面活性剂对模型蛋白的稳定性影响小，但可有效地帮助处于局部能量最低状态的蛋白折叠中间态通过能量壁垒而实现折叠;强疏水性表面活性剂则可与蛋白质形成高稳定性的复合物而阻止折叠的进行，需将其脱除才能使折叠过程重新开始.模拟结果还显示：表面活性剂的加入会使蛋白质折叠中间态更加丰富，从而能够光滑折叠过程中的能量阱;表面活性剂与变性环境对于蛋白质的折叠具有协同效应.模拟结果与文献报道的实验结果具有一致性，显示分子模拟的方法在揭示蛋白质折叠过程的微观机理以及表面活性剂类折叠助剂的分子设计方面有很好的应用前景.

关键词: 分子模拟, HP模型, 表面活性剂, 折叠中间态, 动态Monte Carlo模拟, 蛋白质体外折叠