Institute of High Performance Computing, 1 Fusionopolis Way, #16-16, Connexis, Singapore 138632, Rep. of Singapore.
Phys Chem Chem Phys. 2011 Jan 28;13(4):1649-62. doi: 10.1039/c0cp01509a. Epub 2010 Dec 6.
The solvation of the enzyme Candida antarctica lipase B (CAL-B) was studied in eight different ionic liquids (ILs). The influence of enzyme-ion interactions on the solvation of CAL-B and the structure of the enzyme-IL interface are analyzed. CAL-B and ILs are described with molecular dynamics (MD) simulations in combination with an atomistic empirical force field. The considered cations are based on imidazolium or guanidinium that are paired with nitrate, tetrafluoroborate or hexafluorophosphate anions. The interactions of CAL-B with ILs are dominated by Coulomb interactions with anions, while the second largest contribution stems from van der Waals interactions with cations. The enzyme-ion interaction strength is determined by the ion size and the magnitude of the ion surface charge. The solvation of CAL-B in ILs is unfavorable compared to water because of large formation energies for the CAL-B solute cages in ILs. The internal energy in the IL and of CAL-B increases linearly with the enzyme-ion interaction strength. The average electrostatic potential on the surface of CAL-B is larger in ILs than in water, due to a weaker screening of charged enzyme residues. Ion densities increased moderately in the vicinity of charged residues and decreased close to non-polar residues. An aggregation of long alkyl chains close to non-polar regions and the active site entrance of CAL-B are observed in one IL that involved long non-polar decyl groups. In ILs that contain 1-butyl-3-methylimidazolium cations, the diffusion of one or two cations into the active site of CAL-B occurs during MD simulations. This suggests a possible obstruction of the active site in these ILs. Overall, the results indicate that small ions lead to a stronger electrostatic screening within the solvent and stronger interactions with the enzyme. Also a large ion surface charge, when more hydrophilic ions are used, increases enzyme-IL interactions. An increase of these interactions destabilizes the enzyme and impedes enzyme solvation due to an increase in solute cage formation energies.
研究了八种不同的离子液体（ILs）中酶 Candida antarctica lipase B（CAL-B）的溶剂化作用。分析了酶-离子相互作用对 CAL-B 的溶剂化作用和酶-IL 界面结构的影响。使用分子动力学（MD）模拟结合原子经验力场对 CAL-B 和 ILs 进行了描述。所考虑的阳离子基于咪唑鎓或胍鎓，它们与硝酸盐、四氟硼酸盐或六氟磷酸盐阴离子配对。CAL-B 与 ILs 的相互作用主要由与阴离子的库仑相互作用主导，而第二大贡献来自与阳离子的范德华相互作用。酶-离子相互作用强度取决于离子大小和离子表面电荷的大小。与水相比，CAL-B 在 ILs 中的溶剂化作用是不利的，因为在 ILs 中形成 CAL-B 溶质笼的形成能很大。IL 和 CAL-B 的内能随酶-离子相互作用强度线性增加。由于带电荷的酶残基的屏蔽作用较弱，CAL-B 表面的平均静电势在 ILs 中比在水中更大。由于带电荷的残基附近的离子密度适度增加，而靠近非极性残基的离子密度降低。在一种涉及长非极性癸基的 IL 中，观察到长烷基链在非极性区域附近聚集，并靠近 CAL-B 的活性部位入口。在含有 1-丁基-3-甲基咪唑鎓阳离子的 ILs 中，在 MD 模拟过程中，一个或两个阳离子扩散到 CAL-B 的活性部位。这表明在这些 ILs 中，活性部位可能受阻。总的来说，结果表明，小离子会导致溶剂内的静电屏蔽作用增强，与酶的相互作用增强。当使用更亲水的离子时，较大的离子表面电荷也会增加酶-IL 相互作用。这些相互作用的增加会使酶不稳定，并由于增加溶质笼形成能而阻碍酶的溶剂化。
