Prevost M, Wodak S J, Tidor B, Karplus M
Unité de Conformation des Macromolécules Biologiques, Université Libre de Bruxelles, Brussels, Belgium.
Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10880-4. doi: 10.1073/pnas.88.23.10880.
Molecular dynamics simulations have been used to compute the difference in the unfolding free energy between wild-type barnase and the mutant in which Ile-96 is replaced by alanine. The simulations yield results (-3.42 and -5.21 kcal/mol) that compare favorably with experimental values (-3.3 and -4.0 kcal/mol). The major contributions to the free energy difference arise from bonding terms involving degrees of freedom of the mutated side chain and from nonbonded interactions of that side chain with its environment in the folded protein. By comparison with simulations of an extended peptide in the absence of solvent, used as a reference state, hydration effects are shown to play a minor role in the overall free energy balance for the Ile----Ala transformation. The implications of these results for our understanding of the hydrophobic effect and its contribution to protein stability are discussed.
分子动力学模拟已被用于计算野生型核糖核酸酶 barnase 与异亮氨酸 -96 被丙氨酸取代的突变体之间的解折叠自由能差异。模拟结果（-3.42 和 -5.21 千卡/摩尔）与实验值（-3.3 和 -4.0 千卡/摩尔）相当。自由能差异的主要贡献来自涉及突变侧链自由度的键合项以及该侧链与折叠蛋白环境的非键相互作用。通过与在无溶剂情况下用作参考态的延伸肽模拟进行比较，结果表明水合作用在异亮氨酸向丙氨酸转化的整体自由能平衡中起次要作用。讨论了这些结果对我们理解疏水效应及其对蛋白质稳定性贡献的意义。
