Interplay between binding affinity and kinetics in protein-protein interactions
Interplay between binding affinity and kinetics in protein-protein interactions
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DOI：
10.1002/prot.25041
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发表时间：
2016-07-01
影响因子：
2.9
通讯作者：
Liu, Zhirong
中科院分区：
文献类型：
--
作者：
Cao, Huaiqing;Huang, Yongqi;Liu, Zhirong
为了阐明蛋白质-蛋白质相互作用的结合亲和力和动力学之间的相互作用，以及内在无序的蛋白质在这种相互作用中的可能作用，对20种蛋白质复合物进行了分子模拟。结合偏置电位和重加权技术，得到了生理亲和力下的自由能分布，表明束缚态谷深，势垒高度为12-33 RT。从亲和力对界面相互作用的依赖性来看，熵对结合亲和力的贡献近似与界面面积成正比。提取的解离速率的基础上的阿罗修斯定律与实验值（皮尔逊相关系数R=0.79）相当好。对于每个蛋白质复合物，结合亲和力和解离速率之间的线性自由能关系被证实，但本质上无序的蛋白质的斜率的分布没有表现出本质的差异与观察到的有序蛋白质。还进行了与蛋白质折叠的比较。(C)2016 Wiley Periodicals，Inc.
To clarify the interplay between the binding affinity and kinetics of protein-protein interactions, and the possible role of intrinsically disordered proteins in such interactions, molecular simulations were carried out on 20 protein complexes. With bias potential and reweighting techniques, the free energy profiles were obtained under physiological affinities, which showed that the bound-state valley is deep with a barrier height of 12-33 RT. From the dependence of the affinity on interface interactions, the entropic contribution to the binding affinity is approximated to be proportional to the interface area. The extracted dissociation rates based on the Arrhenius law correlate reasonably well with the experimental values (Pearson correlation coefficient R=0.79). For each protein complex, a linear free energy relationship between binding affinity and the dissociation rate was confirmed, but the distribution of the slopes for intrinsically disordered proteins showed no essential difference with that observed for ordered proteins. A comparison with protein folding was also performed. (C) 2016 Wiley Periodicals, Inc.