Jump to Main Content
Salt-bridge dynamics in intrinsically disordered proteins: A trade-off between electrostatic interactions and structural flexibility Proteins and proteomics
- Basu, Sankar, Biswas, Parbati
- Biochimica et biophysica acta 2018 v.1866 pp. 624-641
- electrostatic interactions, models, proteins
- 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.