Institute for Research in Biomedicine, Joint IRB-BSC Program in Computational Biology, c/Baldiri i Reixac 10-12, 08028 Barcelona, Spain.
Structure. 2011 Jun 8;19(6):881-9. doi: 10.1016/j.str.2011.03.009.
The study of protein binding mechanisms is a major topic of research in structural biology. Here, we implement a combination of metrics to systematically assess the cost of backbone conformational changes that protein domains undergo upon association. Through the analyses of 2090 unique unbound → bound transitions, from over 12,000 structures, we show that two-thirds of these proteins do not suffer significant structural changes upon binding, and could thus fit the lock-and-key model well. Among the remaining proteins, one-third explores the bound conformation in the unbound state (conformational selection model) and, while most transitions are possible from an energetic perspective, a few do require external help to break the thermodynamic barrier (induced fit model). We also analyze the relationship between conformational transitions and protein connectivity, finding that, in general, domains interacting with many partners undergo smaller changes upon association, and are less likely to freely explore larger conformational changes.
蛋白质结合机制的研究是结构生物学的一个主要研究课题。在这里，我们结合使用了多种指标来系统地评估蛋白质结构域在结合时发生的骨架构象变化的代价。通过对 2090 个独特的无约束→约束转变的分析，来自超过 12000 个结构，我们表明，这些蛋白质中有三分之二在结合时没有发生显著的结构变化，因此可以很好地符合锁钥模型。在其余的蛋白质中，三分之一的蛋白质在无约束状态下探索约束构象（构象选择模型），虽然从能量的角度来看大多数转变都是可能的，但有几个转变确实需要外部帮助来打破热力学障碍（诱导契合模型）。我们还分析了构象转变与蛋白质连接性之间的关系，发现通常情况下，与许多伴侣相互作用的结构域在结合时发生的变化较小，并且不太可能自由探索更大的构象变化。
