Proteinprotein interactions: General trends in the relationship between binding affinity and interfacial buried surface area
Proteinprotein interactions: General trends in the relationship between binding affinity and interfacial buried surface area
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DOI：
10.1002/pro.2230
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发表时间：
2013-04-01
期刊：
影响因子：
8
通讯作者：
Regan, Lynne
中科院分区：
文献类型：
--
作者：
Chen, Jieming;Sawyer, Nicholas;Regan, Lynne
蛋白质相互作用在许多细胞过程中起着关键作用，它们的亲和力和特异性与它们所执行的功能密切相关。在此，我们研究了结合亲和力与蛋白质界面的大小和化学性质之间的关系。我们的分析集中在异源二聚体上，包括113个配合物的结构和热力学数据。我们观察到结合亲和度与界面处埋藏的表面积有直接的关系。对于给定的表面积埋藏量，结合亲和力跨越四个数量级的解离常数（Kd）。在整个数据集中，我们观察到结合亲和力和界面的化学成分之间没有明显的关系。我们还计算了每个异二聚体的每单位表面埋埋面积的自由能或表面能密度。当界面面积在500 ~ 2000埃之间时，表面能密度随着埋深面积的增大而减小。当埋藏的表面面积超过2000埃时，表面能量密度趋于恒定。我们相信，这些分析和数据将有助于研究人员理解、设计或抑制蛋白质-蛋白质界面。
Proteinprotein interactions play key roles in many cellular processes and their affinities and specificities are finely tuned to the functions they perform. Here, we present a study on the relationship between binding affinity and the size and chemical nature of proteinprotein interfaces. Our analysis focuses on heterodimers and includes curated structural and thermodynamic data for 113 complexes. We observe a direct correlation between binding affinity and the amount of surface area buried at the interface. For a given amount of surface area buried, the binding affinity spans four orders of magnitude in terms of the dissociation constant (Kd). Across the entire dataset, we observe no obvious relationship between binding affinity and the chemical composition of the interface. We also calculate the free energy per unit surface area buried, or surface energy density, of each heterodimer. For interfacial surface areas between 500 and 2000 angstrom 2, the surface energy density decreases as the buried surface area increases. As the buried surface area increases beyond about 2000 angstrom 2, the surface energy density levels off to a constant value. We believe that these analyses and data will be useful for researchers with an interest in understanding, designing or inhibiting proteinprotein interfaces.