Department of Chemistry, University of Delhi, Viswavidyalay Marg, North Campus, Delhi 110007, India.
Department of Chemistry, University of Delhi, Viswavidyalay Marg, North Campus, Delhi 110007, India.
Biochim Biophys Acta Proteins Proteom. 2018 May-Jun;1866(5-6):624-641. doi: 10.1016/j.bbapap.2018.03.002. Epub 2018 Mar 14.
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.
无规则蛋白质（IDPs）富含带电和极性残基；因此，静电相互作用在其动力学中起主要作用。为了保持多功能性并表现出其特征性的结合混杂性，它们需要保留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，这最终导致形成盐桥，赋予局部刚性。因此，盐桥的形成与所需的动态灵活性相矛盾。因此，这两种机制之间似乎存在着微妙的权衡，本研究试图揭示这种权衡。为此，我们在一组适当选择的 IDP 的分子动力学轨迹中识别和分析盐桥，包括孤立的和复合的离子键基序。研究了这些盐桥的时间演变结构特性，如持久性、相关的二级结构“有序-无序”转变、相关原子运动、对蛋白质整体静电平衡的贡献等，这些都进行了必要的详细研究。结果表明，随着时间的推移，保持这种平衡的关键是广泛持久性的盐桥的连续形成和溶解。此外，在瞬态离子键中带电荷原子对（来自各种带相反电荷的侧链）的连续动态交换支持一种与这些蛋白质中特征性随机构象转换相伴随的动态灵活性模型。这些结果和结论应该有助于未来设计盐桥，以进一步探索蛋白质中无规-球型界面。
