界面几何形状如何决定水在疏水缔合中的热力学特征
How interface geometry dictates water's thermodynamic signature in hydrophobic association
摘要：
一般认为，分子尺度的结合伴侣之间的疏水缔合主要由熵驱动。最近的量热实验和计算机模拟严重挑战这一既定的范例，报告说，水的热力学签名的结合小疏水配体类似大小的非极性口袋是水的驱动。在这里，我们表明，纯粹的几何考虑，这一争议可以得到解决，如果适当考虑到水界面热力学的凹凸弯曲的对抗性影响。这种连续体观点的一个关键预测是，对于凸配体与凹配体的完全互补结合，水显示出与平面（大规模）疏水缔合非常相似的热力学特征，即，水是主导的，并且几乎不依赖于特定的口袋/配体几何形状。最近的模拟数据的详细比较，定性支持我们的观点的有效性下降到亚纳米尺度。我们的研究结果具有重要的意义，在分子识别和缔合过程中发现的热力学签名的解释。此外，传统的隐式溶剂模型可能会受益于我们的观点，就其预测结合自由能和熵的能力。
英文摘要：
As a common view the hydrophobic association between molecular-scale binding partners is supposed to be dominantly driven by entropy. Recent calorimetric experiments and computer simulations heavily challenge this established paradigm by reporting that water's thermodynamic signature in the binding of small hydrophobic ligands to similar-sized apolar pockets is enthalpy-driven. Here we show with purely geometric considerations that this controversy can be resolved if the antagonistic effects of concave and convex bending on water interface thermodynamics are properly taken into account. A key prediction of this continuum view is that for fully complementary binding of the convex ligand to the concave counterpart, water shows a thermodynamic signature very similar to planar (large-scale) hydrophobic association, that is, enthalpy-dominated, and hardly depends on the particular pocket/ligand geometry. A detailed comparison to recent simulation data qualitatively supports the validity of our perspective down to subnanometer scales. Our findings have important implications for the interpretation of thermodynamic signatures found in molecular recognition and association processes. Furthermore, traditional implicit solvent models may benefit from our view with respect to their ability to predict binding free energies and entropies.
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