Hydrophobicity of proteins and nanostructured solutes is governed by topographical and chemical context
Hydrophobicity of proteins and nanostructured solutes is governed by topographical and chemical context
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DOI：
10.1073/pnas.1700092114
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
E. Xi;V. Venkateshwaran;Lijuan Li;Nicholas B Rego;Amish J. Patel;S. Garde
中科院分区：
文献类型：
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作者：
E. Xi;V. Venkateshwaran;Lijuan Li;Nicholas B Rego;Amish J. Patel;S. Garde
意义许多生物自组装过程，从蛋白质折叠到分子识别，都是由疏水相互作用驱动的，然而在纳米尺度上表征疏水性仍然是一个重大挑战，因为它需要了解蛋白质-水相互作用的强度和它们被破坏的容易程度。蛋白质附近的水以一种集体和复杂的方式对其化学和地形做出反应，通常使用的表面积模型或水动力学标度无法捕捉到这种情况。我们证明，蛋白质附近的水密度波动可以表征蛋白质的疏水性，并揭示其在纳米尺度上对曲率和化学模式的依赖关系。我们的方法为理解和有效描述生物分子相互作用开辟了新的途径。疏水相互作用驱动了许多重要的生物分子自组装现象。然而，在纳米尺度上表征疏水性仍然是一个挑战，因为它依赖于生物分子表面的化学和形貌。在这里，我们使用分子模拟和增强采样方法，系统地将水分子从纳米结构溶质的水化壳层中置换出来，并计算界面水密度波动的自由能，从而量化溶质-水粘附的程度，从而确定溶质的疏水性。特别是，我们表征了弯曲的石墨烯薄片、具有化学图案的自组装单分子膜(SAM)和蛋白质疏水蛋白II的突变体的疏水性。我们发现，与平坦或凸面附近相比，凹面非极面附近的水密度涨落增强，这表明凹面更疏水。我们还发现，图案化的自组装膜和蛋白质突变体，具有相同数量的非极性和极性位置，但不同的几何排列，可以显示出显著不同的水附着强度。具体地说，羟基最有效地降低了端甲基自组装膜的疏水性，不是当它们聚集在一起时，而是当它们被一个甲基分开时。疏水蛋白-II突变体表明，当放置在大的非极性贴片的中心而不是边缘时，带电的氨基酸会降低其疏水性。我们的结果强调了基于水密度波动的测量方法在表征纳米尺度表面疏水性方面的威力，并告诫不要使用加法近似，例如常用的表面积模型或疏水标度来表征生物分子的疏水性和相关的组装驱动力。
Significance Numerous biological self-assembly processes, from protein folding to molecular recognition, are driven by hydrophobic interactions, yet characterizing hydrophobicity at the nanoscale has remained a major challenge, because it requires understanding of the strength of protein–water interactions and the ease with which they can be disrupted. Water near a protein responds to its chemistry and topography in a manner that is collective and complex and cannot be captured by commonly used surface area models or hydropathy scales. We demonstrate that water density fluctuations near proteins can characterize protein hydrophobicity and reveal its dependence on curvature and chemical patterns at the nanoscale. Our approach opens new avenues for understanding and efficient characterization of biomolecular interactions. Hydrophobic interactions drive many important biomolecular self-assembly phenomena. However, characterizing hydrophobicity at the nanoscale has remained a challenge due to its nontrivial dependence on the chemistry and topography of biomolecular surfaces. Here we use molecular simulations coupled with enhanced sampling methods to systematically displace water molecules from the hydration shells of nanostructured solutes and calculate the free energetics of interfacial water density fluctuations, which quantify the extent of solute–water adhesion, and therefore solute hydrophobicity. In particular, we characterize the hydrophobicity of curved graphene sheets, self-assembled monolayers (SAMs) with chemical patterns, and mutants of the protein hydrophobin-II. We find that water density fluctuations are enhanced near concave nonpolar surfaces compared with those near flat or convex ones, suggesting that concave surfaces are more hydrophobic. We also find that patterned SAMs and protein mutants, having the same number of nonpolar and polar sites but different geometrical arrangements, can display significantly different strengths of adhesion with water. Specifically, hydroxyl groups reduce the hydrophobicity of methyl-terminated SAMs most effectively not when they are clustered together but when they are separated by one methyl group. Hydrophobin-II mutants show that a charged amino acid reduces the hydrophobicity of a large nonpolar patch when placed at its center, rather than at its edge. Our results highlight the power of water density fluctuations-based measures to characterize the hydrophobicity of nanoscale surfaces and caution against the use of additive approximations, such as the commonly used surface area models or hydropathy scales for characterizing biomolecular hydrophobicity and the associated driving forces of assembly.