Origin of heat capacity changes in a "nonclassical" hydrophobic interaction.
Origin of heat capacity changes in a "nonclassical" hydrophobic interaction.
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DOI：
10.1002/cbic.200700281
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发表时间：
2007-09-03
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Edsall [1]的早期工作阐明了非极性基团在提高水溶液中溶质的表观热容方面的作用。随后，由于在这些基团周围形成结构化水，因此已经很好地建立了疏水效应。[2-5]虽然这种结构的性质仍然是一个争论的话题，[6]但人们普遍认为这些水分子具有比本体水更高的热容和更低的熵。因此，疏水相互作用，其中非极性表面与本体水屏蔽，其典型特征在于有利的熵结合特征以及恒压下热容（ΔCp）的负变化。[3-5尽管如此，后者在有偿付能力的重组中的基础并没有被普遍接受。[8]最近，我们在模型配体-蛋白质相互作用的研究中观察到了一个矛盾的疏水性驱动的热力学结合特征[9]，即重组小鼠主要尿蛋白（rMUP）的疏水结合口袋内的小疏水配体的缔合。[10]在许多疏水分子相互作用中已经观察到这种结合特征（Meyer et al. [11])并导致了“非经典”疏水相互作用的概念。然而，“非经典”和“经典”疏水相互作用之间的热力学关系仍然模糊，特别是因为前者通常表现出后者热容的负变化;这表明，每个的分子基础在于溶剂重组。在rMUP的情况下，我们发现结合口袋是次优水合的，[12]这种现象在其他蛋白质中越来越多地被报道。[13]在这些情况下，在缔合之后的溶质-溶质分散相互作用与缔合之前存在的溶质-溶剂分散相互作用之间存在不平衡。此外，有利的熵的贡献，从溶剂水分子的驱逐结果是小的，并导致一个热力学的结合签名，是焓驱动。[12，14]然而，结合时热容的负变化（ΔCb
The early work of Edsall [1] illustrated the effect of nonpolar groups in raising the apparent heat capacities of solutes in aqueous solution. Subsequently, the hydrophobic effect has been well established as the result of the formation of structured water around such groups.[2–5] While the nature of this structuring remains a topic of debate,[6] it is universally accepted that these water molecules possess a higher heat capacity and a lower entropy than bulk water. Consequently, hydrophobic interactions, in which nonpolar surfaces are shielded from bulk water, are classically characterized by a favourable entropic binding signature together with a negative change in heat capacity at constant pressure (ΔCp).[3–5, 7] Nonetheless, the foundations of the latter in solvent reorganisation are not universally accepted.[8]Recently, we observed a paradoxical enthalpy-driven thermodynamic binding signature [9] in studies on a model ligand–protein interaction, namely the association of small hydrophobic ligands within the hydrophobic binding pocket of recombinant mouse major urinary protein (rMUP).[10] This binding signature has been observed in a number of hydrophobic molecular interactions (reviewed by Meyer et al.[11]) and has led to the concept of the “nonclassical” hydrophobic interaction. However, the thermodynamic relationship between the “nonclassical” and “classical” hydrophobic interaction has remained obscure, especially since the former typically exhibits the negative change in heat capacity of the latter; this suggests that the molecular basis of each lies in solvent reorganization. In the case of rMUP we found that the binding pocket is suboptimally hydrated,[12] a phenomenon that is increasingly being ACHTUNGTRENNUNGreported in other proteins.[13] Under these circumstances, there exists an imbalance between solute–solute dispersion interactions following the association, versus solute–solvent dispersion interactions that exist prior to the association. Moreover, the favourable entropic contribution that results from the expulsion of solvent water molecules is small, and leads to a thermodynamic binding signature that is enthalpy driven.[12, 14] However, a negative change in heat capacity on binding (ΔCb