Restricted mobility of conserved residues in protein-protein interfaces in molecular simulations.
Restricted mobility of conserved residues in protein-protein interfaces in molecular simulations.
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DOI：
10.1529/biophysj.107.114835
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发表时间：
2008-05
影响因子：
3.4
通讯作者：
O. Yogurtçu;S. Erdemli;R. Nussinov;R. Nussinov;M. Turkay;O. Keskin
中科院分区：
文献类型：
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作者：
O. Yogurtçu;S. Erdemli;R. Nussinov;R. Nussinov;M. Turkay;O. Keskin
蛋白质-蛋白质界面中的保守残基与残基热点相关。为了深入了解他们的角色，我们研究了他们的流动性。我们对 15 种配合物及其单体进行了 39 次显式溶剂模拟，其中界面的大小、形状和功能各不相同。未结合单体中保守残基的动态行为表明，与其环境相比，其灵活性显着降低，这表明在结合之前，它们就被限制在类似束缚的构型中。为了理解这种行为，我们分析了链间和链内氢键在界面中的停留时间。我们发现与非保守残基相比，保守残基并未显着参与界面上的氢键。然而，单体模拟表明，保守残基在结合前主要促进氢键形成。结合前后，整个轨迹上保守残基的堆积明显更高，这合理化了它们较低的迁移率。主干扭转角分布表明，保守残基呈现受限的空间区域，并且在结合和未结合轨迹中访问最多的构象是相似的，这表明保守残基是预先组织的。结合之前的研究，我们得出结论，保守残基、热点残基、锚定残基和界面埋藏残基可能是相似的残基，发挥相似的作用。
Conserved residues in protein-protein interfaces correlate with residue hot-spots. To obtain insight into their roles, we have studied their mobility. We have performed 39 explicit solvent simulations of 15 complexes and their monomers, with the interfaces varying in size, shape, and function. The dynamic behavior of conserved residues in unbound monomers illustrates significantly lower flexibility as compared to their environment, suggesting that already before binding they are constrained in a boundlike configuration. To understand this behavior, we have analyzed the inter- and intrachain hydrogen-bond residence-time in the interfaces. We find that conserved residues are not involved significantly in hydrogen bonds across the interface as compared to nonconserved. However, the monomer simulations reveal that conserved residues contribute dominantly to hydrogen-bond formation before binding. Packing of conserved residues across the trajectories is significantly higher before and after the binding, rationalizing their lower mobility. Backbone torsional angle distributions show that conserved residues assume restricted regions of space and the most visited conformations in the bound and unbound trajectories are similar, suggesting that conserved residues are preorganized. Combined with previous studies, we conclude that conserved residues, hot spots, anchor, and interface-buried residues may be similar residues, fulfilling similar roles.