Department of Physics (E22), IMETUM, CeNS, Technische Universität München, Boltzmannstr. 11, 85748 Garching, Germany.
Chemphyschem. 2012 Mar;13(4):982-9. doi: 10.1002/cphc.201100776. Epub 2012 Jan 31.
The hydrophobic attraction (HA) is believed to be one of the main driving forces for protein folding. Understanding its temperature dependence promises a deeper understanding of protein folding. Herein, we present an approach to investigate the HA with a combined experimental and simulation approach, which is complementary to previous studies on the temperature dependence of the solvation of small hydrophobic spherical particles. We determine the temperature dependence of the free-energy change and detachment length upon desorption of single polypeptides from hydrophobic substrates in aqueous environment. Both the atomic force microscopy (AFM) based experiments and the molecular dynamics (MD) simulations show only a weak dependence of the free energy change on temperature. In fact, depending on the substrate, we find a maximum or a minimum in the temperature-dependent free energy change, meaning that the entropy increases or decreases with temperature for different substrates. These observations are in contrast to the solvation of small hydrophobic particles and can be rationalized by a compensation mechanism between the various contributions to the desorption force. On the one hand this is reminiscent of the protein folding process, where large entropic and enthalpic contributions compensate each other to result in a small free energy difference between the folded and unfolded state. On the other hand, the protein folding process shows much stronger temperature dependence, pointing to a fundamental difference between protein folding and adsorption. Nevertheless such temperature dependent single molecule desorption studies open large possibilities to study equilibrium and non-equilibrium processes dominated by the hydrophobic attraction.
疏水吸引（HA）被认为是蛋白质折叠的主要驱动力之一。了解其对温度的依赖关系有望更深入地了解蛋白质折叠。在此，我们提出了一种结合实验和模拟方法来研究 HA 的方法，这与以前关于小疏水分子在水相中的溶剂化的温度依赖性的研究是互补的。我们确定了在水相环境中从疏水底物上解吸单条多肽时，自由能变化和脱离长度随温度的变化。原子力显微镜（AFM）实验和分子动力学（MD）模拟都表明自由能变化对温度的依赖性很弱。实际上，根据不同的基底，我们发现自由能变化的温度依赖性存在最大值或最小值，这意味着对于不同的基底，熵随温度增加或减少。这些观察结果与小疏水分子的溶剂化作用相反，可以通过解吸力的各种贡献之间的补偿机制来解释。一方面，这让人联想到蛋白质折叠过程，其中大的熵和焓贡献相互补偿，导致折叠态和未折叠态之间的自由能差异很小。另一方面，蛋白质折叠过程表现出更强的温度依赖性，表明蛋白质折叠和吸附之间存在根本区别。然而，这种温度依赖的单分子解吸研究为研究由疏水吸引主导的平衡和非平衡过程提供了很大的可能性。
