Identifying hydrophobic protein patches to inform protein interaction interfaces
Identifying hydrophobic protein patches to inform protein interaction interfaces
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DOI：
10.1073/pnas.2018234118
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发表时间：
2021-02-09
影响因子：
11.1
通讯作者：
Patel，Amish J.
中科院分区：
文献类型：
--
作者：
Rego，Nicholas B.;Xi，Erte;Patel，Amish J.
蛋白质之间的相互作用是许多生物过程的核心，对细胞的正常功能至关重要。尽管疏水残基在驱动蛋白质相互作用中的重要性被普遍接受，但蛋白质疏水性的表征，其相互作用的信息，仍然难以捉摸。挑战在于捕获蛋白质水合水对纳米级化学和地形蛋白质模式的集体反应，这些模式决定了蛋白质的疏水性。为了解决这一挑战，我们采用了专门的分子模拟，其中水分子系统地从蛋白质水合壳中位移；通过识别比其他区域更容易放弃水分的蛋白质区域，我们就能够发现最疏水的蛋白质斑块。令人惊讶的是，这样的贴片含有很大一部分极性/带电原子，其化学成分与更亲水的蛋白质贴片相似。重要的是，我们还发现大多数疏水蛋白斑块和介导蛋白质相互作用的区域之间存在惊人的对应关系。因此，我们的工作建立了一个计算框架，用于表征两亲性溶质（如显示纳米级非均质性的蛋白质）的新兴疏水性，并用于揭示它们的相互作用界面。
Interactions between proteins lie at the heart of numerous biological processes and are essential for the proper functioning of the cell. Although the importance of hydrophobic residues in driving protein interactions is universally accepted, a characterization of protein hydrophobicity, which informs its interactions, has remained elusive. The challenge lies in capturing the collective response of the protein hydration waters to the nanoscale chemical and topographical protein patterns, which determine protein hydrophobicity. To address this challenge, here, we employ specialized molecular simulations wherein water molecules are systematically displaced from the protein hydration shell; by identifying protein regions that relinquish their waters more readily than others, we are then able to uncover the most hydrophobic protein patches. Surprisingly, such patches contain a large fraction of polar/charged atoms and have chemical compositions that are similar to the more hydrophilic protein patches. Importantly, we also find a striking correspondence between the most hydrophobic protein patches and regions that mediate protein interactions. Our work thus establishes a computational framework for characterizing the emergent hydrophobicity of amphiphilic solutes, such as proteins, which display nanoscale heterogeneity, and for uncovering their interaction interfaces.