Peptide adsorption on a hydrophobic surface results from an interplay of solvation, surface, and intrapeptide forces
Peptide adsorption on a hydrophobic surface results from an interplay of solvation, surface, and intrapeptide forces
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DOI：
10.1073/pnas.0707879105
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发表时间：
2008-02-26
影响因子：
11.1
通讯作者：
Netz, R. R.
中科院分区：
文献类型：
--
作者：
Horinek, D.;Serr, A.;Netz, R. R.
疏水效应，即分子非极性部分的弱溶剂化，在蛋白质折叠中起着关键作用，更普遍的是在水介质中的分子自组装和聚集中起着关键作用。水结构的扰动解释了蛋白质疏水性的许多方面。然而，分子实体本身之间的色散相互作用在多大程度上起作用仍不清楚。之所以如此，是因为在肽折叠中，相互作用和结构变化发生在所有长度尺度上，并且使得解开各种贡献变得不可能。我们通过实验和理论上解决了这个问题，研究了在水存在的情况下从平坦的疏水性金刚石表面剥离轻度疏水性单肽分子所需的力。这种设置避免了由气泡吸附、空化和缓慢平衡引起的问题，这些问题使经过大量研究的具有两个宏观表面的几何结构变得复杂。使用原子力光谱，我们确定单个蜘蛛丝肽链的平均解吸力为 F = 58 +/- 8 pN，这相当于每个氨基酸的解吸自由能约为 5 k(B)T。我们的全原子分子动力学模拟（包括显式水）相应地产生解吸力 F = 54 +/- 15 pN。这一观察结果表明，经典模拟中使用的标准非极化力场能够解析肽疏水吸引力的细节。对所涉及的能量学的分析表明，水结构效应和色散相互作用的贡献相当大，但基本上相互抵消。由此可见，肽疏水性的正确建模必须考虑溶剂化和分散效应的紧密耦合。
The hydrophobic effect, i.e., the poor solvation of nonpolar parts of molecules, plays a key role in protein folding and more generally for molecular self-assembly and aggregation in aqueous media. The perturbation of the water structure accounts for many aspects of protein hydrophobicity. However, to what extent the dispersion interaction between molecular entities themselves contributes has remained unclear. This is so because in peptide folding interactions and structural changes occur on all length scales and make disentangling various contributions impossible. We address this issue both experimentally and theoretically by looking at the force necessary to peel a mildly hydrophobic single peptide molecule from a flat hydrophobic diamond surface in the presence of water. This setup avoids problems caused by bubble adsorption, cavitation, and slow equilibration that complicate the much-studied geometry with two macroscopic surfaces. Using atomic-force spectroscopy, we determine the mean desorption force of a single spider-silk peptide chain as F = 58 +/- 8 pN, which corresponds to a desorption free energy of approximate to 5 k(B)T per amino acid. Our all-atomistic molecular dynamics simulation including explicit water correspondingly yields the desorption force F = 54 +/- 15 pN. This observation demonstrates that standard nonpolarizable force fields used in classical simulations are capable of resolving the fine details of the hydrophobic attraction of peptides. The analysis of the involved energetics shows that water-structure effects and dispersive interactions give contributions of comparable magnitude that largely cancel out. It follows that the correct modeling of peptide hydrophobicity must take the intimate coupling of solvation and dispersive effects into account.