Power-Law Solvation Dynamics in Human Serum Albumin

Water and ions surrounding biomolecules are not passive background; their reorganisation through electrostatic interactions, so-called solvation dynamics, actively controls the structures and functions of biomolecules. However, understanding the nature of dynamics remains debated. While dynamics in DNA are shown to follow dispersed, power-law relaxation over many decades, protein hydration has typically been described by discrete, multi-exponential decays. Whether this reflects the true structure-dependent difference between DNA and protein solvation, or is simply due to the limited time windows, has been unclear. Here we investigate the dynamics of solvation in human serum albumin (HSA) around its single tryptophan residue (Trp214) located in subdomain IIA, using all-atom molecular dynamics (MD) simulation. We directly compare the simulated dynamics with two fragmented time-resolved fluorescence Stokes shift (TRFSS) experiments reported by other groups, which together span a broad time window of five decades from 100 fs to 10 ns. Simulation and experiments agree remarkably well, showing that solvation response in HSA is best described by a continuous, power-law decay with a scaling exponent of -0.30 spanning 100 fs to <10 ns, contrary to the multi-exponential behaviour. The dynamics resemble that of DNA but are appreciably faster, revealing a glassy nature. Decomposition of the total solvation response into its components’ contributions shows that none of water, ions or protein individually control the powerlaw dynamics; instead, the relaxation emerges from their coupled, cooperative motions, with the water response strongly anticorrelated to that of chloride (Cl - ) ions and protein segments. Complementary analyses of residence times and mean-squared displacements show that hydration water and Cl - ions undergo non-Markovian, subdiffusive motion with broadly distributed activation barriers and transient trapping on a rugged potential energy landscape. Our results show that solvation dynamics in HSA, like those in DNA, are intrinsically dispersed and glassy in character, leading to a power-law decay, where mobile counterions also contribute to the protein hydration dynamics. This work provides a unified microscopic framework for interpreting protein solvation and motivates further studies on other proteins to find its generality.