PROTEIN FOLDING AND ASSOCIATION - INSIGHTS FROM THE INTERFACIAL AND THERMODYNAMIC PROPERTIES OF HYDROCARBONS
PROTEIN FOLDING AND ASSOCIATION - INSIGHTS FROM THE INTERFACIAL AND THERMODYNAMIC PROPERTIES OF HYDROCARBONS
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DOI：
10.1002/prot.340110407
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发表时间：
1991-01-01
影响因子：
2.9
通讯作者：
HONIG, B
中科院分区：
文献类型：
--
作者：
NICHOLLS, A;SHARP, KA;HONIG, B
在这项工作中，我们证明了表面张力、水-有机溶剂、无转移能和直链烷烃熔融的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的见解。我们首先建立了疏水效应与曲率相关的模型，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众所周知的关系，揭示了分散力在疏水相互作用中几乎或没有净作用；相反，水结构破坏的标准模型(在25摄氏度时以熵驱动)是正确的。疏水相互作用被发现，与经典图像一致，为蛋白质折叠提供了主要推动力。对碳氢化合物熔融行为的分析表明，蛋白质内部的紧密堆积对折叠只有很小的自由能贡献，因为侧链运动的冻结抵消了(相对于液体)分散相互作用增加所产生的焓增加。在缔合反应中应该出现相同的效果，这可以在结合能的计算中提供极大的简化。蛋白质结合反应，甚至在近平面或凹/凸界面之间的结合反应，被发现具有比基于宏观表面张力的预测小得多的有效疏水性。这是由于形成了一个凹陷的领区，通常伴随着复杂的形成。这种效应可以防止在凸面之间形成复合体。
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.