Abstract
Protein and water dynamics have a synergistic relationship, which is particularly important for intrinsically disordered proteins (IDPs), although the details of this coupling remain poorly understood. Here, we combine temperature-dependent molecular dynamics simulations using different water models with extensive nuclear magnetic resonance (NMR) relaxation to examine the importance of distinct modes of solvent and solute motion for the accurate reproduction of site-specific dynamics in IDPs. We find that water dynamics play a key role in motional processes internal to "segments" of IDPs, stretches of primary sequence that share dynamic properties and behave as discrete dynamic units. We identify a relationship between the time scales of intrasegment dynamics and the lifetime of hydrogen bonds in bulk water. Correct description of these motions is essential for accurate reproduction of protein relaxation. Our findings open important perspectives for understanding the role of hydration water on the behavior and function of IDPs in solution.