摘要
蛋白-蛋白相互作用(Protein-protein interaction,PPI)广泛存在于生物体内的分子识别过程中,并且参与调节绝大多数的细胞功能。精确地调控蛋白-蛋白相互作用中的热力学与动力学对于正常的生理功能至关重要。我们通过对20个蛋白质相互作用复合物进行粗粒化的分子动力学模拟,研究了不同体系结合亲和性(Binding affinity)与结合动力学(Binding kinetics)之间的相关性,并得到了一系列普遍结果。这些体系结合-解离过程的势垒在12-33 RT之间,其结合亲和力的熵贡献与复合物结合界面的面积近似成正比,以及我们在每个体系中都确认了亲和性-动力学线性相关性的存在。对于我们研究的出发点——亲和性-动力学的关联与蛋白质结构有序性是否相关,我们发现上述线性相关性的斜率分布并没有明显的有序和无序差异。
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.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.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.
引文
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