Salt-bridge dynamics in intrinsically disordered proteins: A trade-off between electrostatic interactions and structural flexibility
Salt-bridge dynamics in intrinsically disordered proteins: A trade-off between electrostatic interactions and structural flexibility
复制标题
DOI：
10.1016/j.bbapap.2018.03.002
复制
发表时间：
2018-05-01
影响因子：
3.2
通讯作者：
Biswas, Parbati
中科院分区：
文献类型：
--
作者：
Basu, Sankar;Biswas, Parbati
内在无序蛋白（IDPs）富含带电残基和极性残基；因此，静电相互作用在它们的动力学中起着主导作用。为了保持多功能性并表现出绑定混杂的特性，它们需要保持相当大的动态灵活性。同时，它们还需要容纳大量带相反电荷的残基，这最终导致盐桥的形成，从而赋予局部刚性。因此，盐桥的形成与期望的动态灵活性背道而驰。因此，在这两种机制之间似乎存在一种细致的权衡，这是当前研究试图揭示的。有了这个目标，我们在一组适当选择的IDPs的分子动力学轨迹中识别和分析了盐桥，无论是孤立的还是复合的离子键基序。随着时间的推移，这些盐桥的结构特性，如持久性，相关的二级结构“有序-无序”转变，相关的原子运动，对蛋白质整体静电平衡的贡献已经进行了必要的详细研究。结果表明，随着时间的推移，维持这种权衡的关键是盐桥的持续形成和溶解，并且具有广泛的持久性。此外，在瞬态离子键中，带电原子对（来自各种带相反电荷的侧链）的连续动态交换支持了动态柔韧性模型，该模型伴随着这些蛋白质中具有良好特征的随机构象转换。这些结果和结论将有助于未来盐桥的设计，作为进一步探索蛋白质中无序球形界面的手段。
Intrinsically Disordered Proteins (IDPs) are enriched in charged and polar residues; and, therefore, electrostatic interactions play a predominant role in their dynamics. In order to remain multi-functional and exhibit their characteristic binding promiscuity, they need to retain considerable dynamic flexibility. At the same time, they also need to accommodate a large number of oppositely charged residues, which eventually lead to the formation of salt-bridges, imparting local rigidity. The formation of salt-bridges therefore opposes the desired dynamic flexibility. Hence, there appears to be a meticulous trade-off between the two mechanisms which the current study attempts to unravel. With this objective, we identify and analyze salt-bridges, both as isolated as well as composite ionic bond motifs, in the molecular dynamic trajectories of a set of appropriately chosen IDPs. Time evolved structural properties of these salt-bridges like persistence, associated secondary structural 'order-disorder' transitions, correlated atomic movements, contribution in the overall electrostatic balance of the proteins have been studied in necessary detail. The results suggest that the key to maintain such a trade-off over time is the continuous formation and dissolution of salt-bridges with a wide range of persistence. Also, the continuous dynamic interchange of charged-atom-pairs (coming from a variety of oppositely charged side-chains) in the transient ionic bonds supports a model of dynamic flexibility concomitant with the well characterized stochastic conformational switching in these proteins. The results and conclusions should facilitate the future design of salt-bridges as a mean to further explore the disordered-globular interface in proteins.