Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
J Chem Phys. 2013 Sep 21;139(11):115102. doi: 10.1063/1.4821588.
The structure stability of three α-helix bundle (the B domain of protein A) in an imidazolium-based ionic liquid (1-butyl-3-methylimidazolium chloride (BMIM-Cl)) is studied by molecular dynamics simulations. Consistent with previous experiments, the present simulation results show that the native structure of the protein is consistently stabilized in BMIM-Cl solutions with different concentrations. It is observed that BMIM(+) cations have a strong tendency to accumulate on protein surface whereas Cl(-) anions are expelled from protein. BMIM(+) cations cannot only have electrostatic interactions with the carbonyl groups on backbone and the carboxylate groups on negatively charged side chains, but also have hydrophobic interactions with the side chains of non-polar residues. In the meanwhile, the accumulation of large-size BMIM(+) cations on protein surface could remove the surrounding water molecules, reduce the hydrogen bonding from water to protein, and thus stabilize the backbone hydrogen bonds. In summary, the present study could improve our understanding of the molecular mechanism of the impact of water-miscible ionic liquid on protein structure.
采用分子动力学模拟研究了三种α-螺旋束（蛋白 A 的 B 结构域）在咪唑基离子液体（1-丁基-3-甲基咪唑氯盐（BMIM-Cl））中的结构稳定性。与先前的实验一致，本模拟结果表明，在不同浓度的 BMIM-Cl 溶液中，蛋白质的天然结构始终得到稳定。结果表明，BMIM(+)阳离子强烈倾向于聚集在蛋白质表面，而 Cl(-)阴离子则被排斥出蛋白质。BMIM(+)阳离子不仅可以与骨架上的羰基和带负电荷的侧链上的羧基基团发生静电相互作用，而且还可以与非极性残基的侧链发生疏水相互作用。同时，大尺寸的 BMIM(+)阳离子在蛋白质表面的聚集可以去除周围的水分子，减少来自水分子的氢键与蛋白质的作用，从而稳定骨架氢键。总之，本研究可以增进我们对水混溶性离子液体对蛋白质结构影响的分子机制的理解。
