Nicholls A, Sharp K A, Honig B
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032.
Proteins. 1991;11(4):281-96. doi: 10.1002/prot.340110407.
We demonstrate in this work that the surface tension, water-organic solvent, transfer-free energies and the thermodynamics of melting of linear alkanes provide fundamental insights into the nonpolar driving forces for protein folding and protein binding reactions. We first develop a model for the curvature dependence of the hydrophobic effect and find that the macroscopic concept of interfacial free energy is applicable at the molecular level. Application of a well-known relationship involving surface tension and adhesion energies reveals that dispersion forces play little or no net role in hydrophobic interactions; rather, the standard model of disruption of water structure (entropically driven at 25 degrees C) is correct. The hydrophobic interaction is found, in agreement with the classical picture, to provide a major driving force for protein folding. Analysis of the melting behavior of hydrocarbons reveals that close packing of the protein interior makes only a small free energy contribution to folding because the enthalpic gain resulting from increased dispersion interactions (relative to the liquid) is countered by the freezing of side chain motion. The identical effect should occur in association reactions, which may provide an enormous simplification in the evaluation of binding energies. Protein binding reactions, even between nearly planar or concave/convex interfaces, are found to have effective hydrophobicities considerably smaller than the prediction based on macroscopic surface tension. This is due to the formation of a concave collar region that usually accompanies complex formation. This effect may preclude the formation of complexes between convex surfaces.
在本研究中，我们证明了线性烷烃的表面张力、水 - 有机溶剂、转移自由能以及熔化热力学为蛋白质折叠和蛋白质结合反应的非极性驱动力提供了基本见解。我们首先建立了一个关于疏水效应曲率依赖性的模型，发现界面自由能的宏观概念在分子水平上是适用的。应用一个涉及表面张力和粘附能的著名关系式表明，色散力在疏水相互作用中几乎不发挥净作用或根本不发挥作用；相反，水结构破坏的标准模型（在25摄氏度时由熵驱动）是正确的。与经典观点一致，发现疏水相互作用为蛋白质折叠提供了主要驱动力。对烃类熔化行为的分析表明，蛋白质内部的紧密堆积对折叠仅产生很小的自由能贡献，因为增加的色散相互作用（相对于液体）所带来的焓增被侧链运动的冻结所抵消。在缔合反应中应该会出现相同的效应，这可能会极大地简化结合能的评估。发现蛋白质结合反应，即使是在近乎平面或凹/凸界面之间，其有效疏水性也远小于基于宏观表面张力的预测值。这是由于通常伴随复合物形成而形成的凹形环区域。这种效应可能会阻止凸面之间形成复合物。
