Distinguishing dynamical features of water inside protein hydration layer: Distribution reveals what is hidden behind the average

Abstract

Since the pioneering works of Pethig, Grant and Wüthrich on protein hydration layer, many studies have been devoted to find out if there are any "general and universal" characteristic features that can distinguish water molecules inside the protein hydration layer from bulk. Given that the surface itself varies from protein to protein, and that each surface facing the water is heterogeneous, search for universal features has been elusive.Here, we perform atomistic molecular dynamics simulation in order to propose and demonstrate that such defining characteristics can emerge if we look not at average properties but the distribution of relaxation times. We present results of calculations of distributions of residence times and rotational relaxation times for four different proteinwater systems, and compare them with the same quantities in the bulk. The distributions in the hydration layer is unusually broad and log-normal in nature, due to the simultaneous presence of peptide backbones that form weak hydrogen bonds, hydrophobic amino acid side chains that form no hydrogen bond and charged polar groups that form strong hydrogen bond with the surrounding water molecules. The broad distribution is responsible for the non-exponential dielectric response and also agrees with large specific heat of the hydration water. Our calculations reveal that while the average time constant is just about 2-3 times larger than that of bulk water, it provides a poor representation of the real behaviour. In particular, the average leads to the erroneous conclusion that water in the hydration layer is bulk-like. However, the observed and calculated lower value of static dielectric constant of hydration layer remained difficult to reconcile with the broad distribution observed in dynamical properties. We offer a plausible explanation of these unique properties.

Structural and dynamical heterogeneity of water trapped inside Na+-pumping KR2 rhodopsin in the dark state

“…The rotational motion of water on biological surface is slowed down compared to that in the bulk. 30,[70][71][72] We find a similar slowing down for the water molecules inside cavity. In addition, we observed that the rotational motion inside protein cavity is highly anisotropic with the rotation of the dipole moment vector being the slowest among all the three orthogonal vectors (Fig.…”

Computational discovery of chemically patterned surfaces that effect unique hydration water dynamics

“…For example, large hydrophobic patches at protein surfaces can induce large fluctuations in nearby water density (18), strengthening and accelerating protein−protein association (19). More generally, spatial heterogeneity in hydration shell dynamics, influenced by local geometry and chemical patterning, is a hallmark of proteins of all sizes and functions (20,21). Recent experimental measurements have also shown that such heterogeneity is unique to the folded, structured protein and does not appear in corresponding peptide fragments or intrinsically disordered proteins, suggesting the importance of spatially organized heterogeneity in the well-defined folded structure (5).…”

Hydrogen‐Bond Dynamics and Energetics of Biological Water

“…The energetic distribution across the different types of biological water indicates a larger specific heat for the hydration layer compared to bulk, and this in turn may help stabilize protein structures by minimizing temperature fluctuations in the protein-associated water. [68] All ultrafast physicochemical phenomena investigated to elucidate the dynamics and energetics of biological water, such as solvation dynamics, excited-state proton transfer, and depolarization dynamics, depend on different aspects of the hydration environment surrounding a fluorophore, including the local polarity, H-bond network, and micro-viscosity of the medium. The most important aspect that should be considered, while designing experiments to understand the dynamics of biological water, is the need to minimize any perturbation of the biological structures caused by the incorporation of the probe into the system.…”

“…Using several proteins that were chosen for the diversity of their structure, function, and helix-sheet ratio, Mukherjee et al showed how the broad distribution of residence times and rotation relaxation times of water molecules within the protein hydration layer is responsible for the non-exponential nature of the dielectric response often observed for biological water. [68][69][70][71] Water molecules bound to peptide backbones around hydrophobic residues can be more mobile than bulk water molecules. In contrast, those bound to charged amino acid groups show substantial retardation of the associated dynamics.…”