van Gunsteren W F, Karplus M
Biochemistry. 1982 May 11;21(10):2259-74. doi: 10.1021/bi00539a001.
The effect of a solvent and a crystalline environment on the dynamics of proteins is investigated by the method of computer simulation. Three 25-ps molecular dynamics simulations at 300 K of the bovine pancreatic trypsin inhibitor (BPTI), consisting of 454 heavy atoms, are compared: one of BPTI in vacuo, one of BPTI in a box with 2647 spherical nonpolar solvent atoms, and one of BPTI surrounded by fixed crystal image atoms. Both average and time-dependent molecular properties are examined to determine the effect of the environment on the behavior of the protein. The dynamics of BPTI in solution or in the crystal environment are found to be very similar to that found in the vacuum calculation. The primary difference in the average properties is that the equilibrium structure in the presence of solvent or the crystal field is significantly closer to the X-ray structure than is the vacuum result; concomitantly, the more realistic environment leads to a number density closer to experiment. The presence of solvent has a negligible effect on the overall magnitude of the positional or dihedral angle fluctuations in the interior of the protein; however, there are changes in the decay times of the fluctuations of interior atoms. For surface residues, both the magnitude and the time course of the motions are significantly altered by the solvent. There tends to be an increase in the displacements of long side chains and the flexible parts of the main chain that protrude into the solvent. Further, these motions tend to have a more diffusive character with longer relaxation times than in vacuo. The crystal environment has a specific effect on a number of side chains which are held in relatively fixed positions through hydrogen-bond and electric interactions with the neighboring protein atoms. Most of the effects of the solution environment seem to be sufficiently nonspecific that it may be possible to model them by applying a mean field and stochastic dynamic methods.
通过计算机模拟方法研究了溶剂和晶体环境对蛋白质动力学的影响。比较了由454个重原子组成的牛胰蛋白酶抑制剂（BPTI）在300 K下进行的三次25皮秒分子动力学模拟：一次是BPTI在真空中，一次是BPTI在含有2647个球形非极性溶剂原子的盒子中，还有一次是BPTI被固定的晶体图像原子包围。研究了平均分子性质和随时间变化的分子性质，以确定环境对蛋白质行为的影响。发现BPTI在溶液或晶体环境中的动力学与真空中计算的动力学非常相似。平均性质的主要差异在于，在存在溶剂或晶体场的情况下，平衡结构比真空结果更接近X射线结构；相应地，更逼真的环境导致数密度更接近实验值。溶剂的存在对蛋白质内部位置或二面角波动的总体幅度影响可忽略不计；然而，内部原子波动的衰减时间有所变化。对于表面残基，溶剂显著改变了运动的幅度和时间进程。伸向溶剂中的长侧链和主链柔性部分的位移往往会增加。此外，这些运动往往比在真空中具有更扩散的特征，且弛豫时间更长。晶体环境对一些通过与相邻蛋白质原子的氢键和电相互作用而保持在相对固定位置的侧链有特定影响。溶液环境的大多数影响似乎足够非特异性，以至于有可能通过应用平均场和随机动力学方法对其进行建模。
