Peters G H, van Aalten D M, Edholm O, Toxvaerd S, Bywater R
Chemistry Department III, H.C. Orsted Institutet, University of Copenhagen, Denmark.
Biophys J. 1996 Nov;71(5):2245-55. doi: 10.1016/S0006-3495(96)79428-6.
We have investigated the effect of different solvents on the dynamics of Rhizomucor miehei lipase. Molecular dynamics simulations were performed in water, methyl hexanoate, and cyclohexane. Analysis of the 400-ps trajectories showed that the solvent has a pronounced effect on the geometrical properties of the protein. The radius of gyration and total accessibility surface decrease in organic solvents, whereas the number of hydrogen bonds increases. The essential motions of the protein in different solvents can be described in a low-dimensional "essential subspace," and the dynamic behavior in this subspace correlates with the polarity of the solvent. Methyl hexanoate, which is a substrate for R. miehei lipase, significantly increases the fluctuations in the active-site loop. During the simulation, a methyl hexanoate entered the active-site groove. This observation provides insight into the possible docking mechanism of the substrate.
我们研究了不同溶剂对米黑根毛霉脂肪酶动力学的影响。在水、己酸甲酯和环己烷中进行了分子动力学模拟。对400皮秒轨迹的分析表明，溶剂对蛋白质的几何性质有显著影响。在有机溶剂中，回转半径和总可及表面积减小，而氢键数量增加。蛋白质在不同溶剂中的基本运动可以在一个低维的“基本子空间”中描述，并且该子空间中的动态行为与溶剂的极性相关。作为米黑根毛霉脂肪酶底物的己酸甲酯显著增加了活性位点环的波动。在模拟过程中，一个己酸甲酯分子进入了活性位点凹槽。这一观察结果为底物的可能对接机制提供了见解。
