Heat capacity effects in protein folding and ligand binding: a re-evaluation of the role of water in biomolecular thermodynamics
Heat capacity effects in protein folding and ligand binding: a re-evaluation of the role of water in biomolecular thermodynamics
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DOI：
10.1016/j.bpc.2004.12.011
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Cooper, A
中科院分区：
文献类型：
--
作者：
Cooper, A
大的“反常”热容（Delta C-p）效应是水溶液中生物分子相互作用的热力学的一个共同特征，并且由于直接量热测量设施的改进，关于蛋白质折叠、蛋白质-蛋白质和蛋白质-配体相互作用中的这种效应的实验数据越来越多。传统上，这种热容效应被归因于疏水相互作用，并且有一些非常令人信服的证据证明了这个概念的有用性。尽管如此，也有越来越多的证据表明疏水相互作用并不是这种效应的唯一可能来源。在这里，我们重新评估其他相互作用对协同生物分子折叠和结合过程预期的热容变化的可能贡献，特别是氢键和溶剂水相互作用的作用。基于水的氢键倾向随温度变化的简单模型给出了 Delta C-p 的定量估计，该估计与蛋白质折叠和配体结合的实验观察结果相比较。还估计了蛋白质复合物中结合水的热力学贡献。根据简单晶格模型的预测，络合物中水的捕获应产生更多的放热结合（Delta Delta H-6 至 -12 kJ mol(-1)），每个水分子具有较低的熵（Delta Delta S-0 近似于 11 J mol(-1) K-1）和更负的 Delta C-p（约 -75 J mol(-1) K-1）。更一般地说，很明显，任何涉及多种合作弱相互作用（无论何种类型）的大分子过程都会产生显着的 Delta C-p 效应。 (c) 2004 Elsevier B.V. 保留所有权利。
Large "anomalous" heat capacity (Delta C-p) effects are a common feature of the thermodynamics of biomolecular interactions in aqueous solution and, as a result of the improved facility for direct calorimetric measurements, there is a growing body of experimental data for such effects in protein folding, protein-protein and protein-ligand interactions. Conventionally such heat capacity effects have been ascribed to hydrophobic interactions, and there are some remarkably convincing demonstrations of the usefulness of this concept. Nonetheless, there is also increasing evidence that hydrophobic interactions are not the only possible source of such effects. Here we re-evaluate the possible contributions of other interactions to the heat capacity changes to be expected for cooperative biomolecular folding and binding processes, with particular reference to the role of hydrogen bonding and solvent water interactions. Simple models based on the hydrogen-bonding propensity of water as a function of temperature give quantitative estimates of Delta C-p that compare well with experimental observations for both protein folding and ligand binding. The thermodynamic contribution of bound waters in protein complexes is also estimated. The prediction from simple lattice models is that trapping of water in a complex should give more exothermic binding (Delta Delta H-6 to -12 kJ mol(-1)) with lower entropy (Delta Delta S-0 approximate to 11 J mol(-1) K-1) and more negative Delta C-p (by about -75 J mol(-1) K-1) per water molecule. More generally, it is clear that significant Delta C-p effects are to be expected for any macromolecular process involving a multiplicity of cooperative weak interactions of whatever kind. (c) 2004 Elsevier B.V. All rights reserved.