Unraveling Hydrophobic Interactions at the Molecular Scale Using Force Spectroscopy and Molecular Dynamics Simulations.
Unraveling Hydrophobic Interactions at the Molecular Scale Using Force Spectroscopy and Molecular Dynamics Simulations.
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DOI：
10.1021/acsnano.6b06360
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发表时间：
2017-03
期刊：
影响因子：
17.1
通讯作者：
P. Stock;Jacob I. Monroe;Thomas Utzig;David J Smith;M. Shell;M. Valtiner
中科院分区：
文献类型：
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作者：
P. Stock;Jacob I. Monroe;Thomas Utzig;David J Smith;M. Shell;M. Valtiner
疏水部分之间的相互作用引导水介质中普遍存在的过程，包括生物物质的自组织。近几十年来，在理解宏观疏水界面方面取得了巨大进展。然而，它仍然是一个挑战，实验测量疏水相互作用（HI）在单分子尺度，从而与理论比较。在这里，我们提出了一种结合实验模拟的方法来直接测量和量化的序列依赖性和加和性的肽系统中的HI在单分子尺度。我们结合联合收割机动态单分子力谱模型肽完全原子，平衡和非平衡，分子动力学（MD）模拟相同的系统。具体而言，我们用增加数量的疏水性亮氨酸单体突变柔性（GS）5肽支架，并测量肽从疏水性自组装单层表面的解吸。基于非平衡工作轨迹的分析，我们测量的相互作用的自由能，与3.0-3.4 kBT每亮氨酸线性缩放。在良好的一致性，模拟表明类似的趋势与2.1 kBT每亮氨酸，同时也提供了一个详细的分子视图到HI。这种方法可能提供了一个路线图，直接提取定性和定量的单分子相互作用在固/液界面在广泛的领域，包括在生物界面的相互作用和粘合剂在工业应用中的相互作用。
Interactions between hydrophobic moieties steer ubiquitous processes in aqueous media, including the self-organization of biologic matter. Recent decades have seen tremendous progress in understanding these for macroscopic hydrophobic interfaces. Yet, it is still a challenge to experimentally measure hydrophobic interactions (HIs) at the single-molecule scale and thus to compare with theory. Here, we present a combined experimental-simulation approach to directly measure and quantify the sequence dependence and additivity of HIs in peptide systems at the single-molecule scale. We combine dynamic single-molecule force spectroscopy on model peptides with fully atomistic, both equilibrium and nonequilibrium, molecular dynamics (MD) simulations of the same systems. Specifically, we mutate a flexible (GS)5 peptide scaffold with increasing numbers of hydrophobic leucine monomers and measure the peptides' desorption from hydrophobic self-assembled monolayer surfaces. Based on the analysis of nonequilibrium work-trajectories, we measure an interaction free energy that scales linearly with 3.0-3.4 kBT per leucine. In good agreement, simulations indicate a similar trend with 2.1 kBT per leucine, while also providing a detailed molecular view into HIs. This approach potentially provides a roadmap for directly extracting qualitative and quantitative single-molecule interactions at solid/liquid interfaces in a wide range of fields, including interactions at biointerfaces and adhesive interactions in industrial applications.