Wade R C, Mazor M H, McCammon J A, Quiocho F A
Department of Chemistry, University of Houston, Texas 77204-5641.
Biopolymers. 1991 Jul;31(8):919-31. doi: 10.1002/bip.360310802.
The structure and activity of a protein molecule are strongly influenced by the extent of hydration of its cavities. This is, in turn, related to the free energy change on transfer of a water molecule from bulk solvent into a cavity. Such free energy changes have been calculated for two cavities in a sulfate-binding protein. One of these cavities contains a crystallographically observed water molecule while the other does not. Thermodynamic integration and perturbation methods were used to calculate free energies of hydration for each of the cavities from molecular dynamics simulations of two separate events: the removal of a water molecule from pure water, and the introduction of a water molecule into each protein cavity. From the simulations for the pure water system, the excess chemical potential of water was computed to be -6.4 +/- 0.4 kcal/mol, in accord with experiment and with other recent theoretical calculations. For the protein cavity containing an experimentally observed water molecule, the free energy change on hydrating it with one water molecule was calculated as -10.0 +/- 1.3 kcal/mol, indicating the high probability that this cavity is occupied by a water molecule. By contrast, for the cavity in which no water molecules were experimentally observed, the free energy change on hydrating it with one water molecule was calculated as 0.2 +/- 1.5 kcal/mol, indicating its low occupancy by water. The agreement of these results with experiment suggests that thermodynamic simulation methods may become useful for the prediction and analysis of internal hydration in proteins.
蛋白质分子的结构和活性受其空穴水合程度的强烈影响。反过来，这又与水分子从本体溶剂转移到空穴时的自由能变化有关。已针对硫酸结合蛋白中的两个空穴计算了此类自由能变化。其中一个空穴含有一个晶体学观测到的水分子，而另一个则没有。采用热力学积分和微扰方法，通过两个独立事件的分子动力学模拟来计算每个空穴的水合自由能：从纯水中移除一个水分子，以及将一个水分子引入每个蛋白质空穴。从纯水系统的模拟中，计算得出水的过量化学势为-6.4±0.4千卡/摩尔，这与实验结果以及其他近期的理论计算结果一致。对于含有实验观测到的水分子的蛋白质空穴，用一个水分子对其进行水合时的自由能变化计算为-10.0±1.3千卡/摩尔，这表明该空穴被水分子占据的可能性很高。相比之下，对于未实验观测到水分子的空穴，用一个水分子对其进行水合时的自由能变化计算为0.2±1.5千卡/摩尔，这表明其被水占据的程度较低。这些结果与实验的一致性表明，热力学模拟方法可能对蛋白质内部水合的预测和分析有用。
