Finney J L, Gellatly B J, Golton I C, Goodfellow J
Biophys J. 1980 Oct;32(1):17-33. doi: 10.1016/S0006-3495(80)84913-7.
Using detailed hydrogen bonding, surface exposure, internal environment, and solvent interaction calculations on several proteins, in conjunction wit data from quantum mechanical hydrogen-bonding studies, various contributions to the free energy of globular estimated and their likely relative significance discussed. A picture emerges of globular proteins as extremely well-fitting jigsaw-puzzles, in which no single driving force dominates the marginal stability of the native conformation. Rather, the folded structure is seen as the result of a complex global maximization of several strongly-interacting driving forces. In particular, the necessity to maintain very efficient internal hydrogen-bonding, and the role of the solvent as a hydrogen-bond sink, are stressed as strong constraints on the (incomplete) maximization of hydrophobic effects. The possible significance of internal dipole-induced dipole interactions is discussed tentatively. Although quantitative estimates of the various contributions remain uncertain, consideration of effective force constants suggests that polar, including solvent, interactions may largely determine the overall curvatures of the native conformation's potential well, and be important in controlling the flexibility of local regions which are important for the exact positioning of groups during enzyme catalysis, as well as the molecule's overall dynamics. In contrast, hydrophobic interactions change less for small geometrical perturbations, and seem more relevant to directing the folding protein. along a path to a region in configurational space where the polar interactions can switch on for the final "docking".
通过对几种蛋白质进行详细的氢键、表面暴露、内部环境和溶剂相互作用计算，并结合量子力学氢键研究的数据，估算了对球状蛋白自由能的各种贡献，并讨论了它们可能的相对重要性。由此呈现出球状蛋白是极其契合的拼图的画面，其中没有单一驱动力主导天然构象的边际稳定性。相反，折叠结构被视为几种强相互作用驱动力复杂全局最大化的结果。特别强调了维持非常有效的内部氢键的必要性以及溶剂作为氢键受体的作用，它们是对疏水效应（不完全）最大化的强烈限制。初步讨论了内部偶极诱导偶极相互作用的可能重要性。尽管对各种贡献进行定量估计仍然不确定，但对有效力常数的考虑表明，包括溶剂在内的极性相互作用可能在很大程度上决定天然构象势阱的整体曲率，并且在控制局部区域的灵活性方面很重要，这些局部区域对于酶催化过程中基团的精确定位以及分子的整体动力学都很重要。相比之下，疏水相互作用对于小的几何扰动变化较小，似乎与指导折叠蛋白沿着一条路径到达构型空间中的一个区域更相关，在该区域极性相互作用可以开启以进行最终的“对接”。
