How proteins modify water dynamics

Abstract

Much of biology happens at the protein-water interface, so all dynamical processes in this region are of fundamental importance. Local structural fluctuations in the hydration layer can be probed by O magnetic relaxation dispersion (MRD), which, at high frequencies, measures the integral of a biaxial rotational time correlation function (TCF)-the integral rotational correlation time. NumerousO MRD studies have demonstrated that this correlation time, when averaged over the first hydration shell, is longer than in bulk water by a factor 3-5. This rotational perturbation factor (RPF) has been corroborated by molecular dynamics simulations, which can also reveal the underlying molecular mechanisms. Here, we address several outstanding problems in this area by analyzing an extensive set of molecular dynamics data, including four globular proteins and three water models. The vexed issue of polarity versus topography as the primary determinant of hydration water dynamics is resolved by establishing a protein-invariant exponential dependence of the RPF on a simple confinement index. We conclude that the previously observed correlation of the RPF with surface polarity is a secondary effect of the correlation between polarity and confinement. Water rotation interpolates between a perturbed but bulk-like collective mechanism at low confinement and an exchange-mediated orientational randomization (EMOR) mechanism at high confinement. The EMOR process, which accounts for about half of the RPF, was not recognized in previous simulation studies, where only the early part of the TCF was examined. Based on the analysis of the experimentally relevant TCF over its full time course, we compare simulated and measured RPFs, finding a 30% discrepancy attributable to force field imperfections. We also compute the full O MRD profile, including the low-frequency dispersion produced by buried water molecules. Computing a local RPF for each hydration shell, we find that the perturbation decays exponentially with a decay "length" of 0.3 shells and that the second and higher shells account for a mere 3% of the total perturbation measured byO MRD. The only long-range effect is a weak water alignment in the electric field produced by an electroneutral protein (not screened by counterions), but this effect is negligibly small for O MRD. By contrast, we find that theO TCF is significantly more sensitive to the important short-range perturbations than the other two TCFs examined here.

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.…”

Fundamental limitations of the time-dependent Stokes shift for investigating protein hydration dynamics

“…The computational retardation factors (RF) in this study with respect to the relaxation time of free lysine in water (t bulk = 0.21 ps) are all above 100 (cf. observed via NQR experiments [1][2][3][4][5] and MD simulations [6][7][8][9][10][11][12] as well as the relevant peak in DRS. 18,19 Fig .…”

“…Overall, these values fit the picture of protein hydration dynamics as reported by a range of experiments and simulations much better than the total TDSS. [1][2][3][4][5][6][7][8][9][10][11][12]18,19 Furthermore, please note that the correlation between t cons and t tot is insignificant (R o 0.25). In other words, the character of local hydration dynamics is obscured by the influence of protein motion and is thus not reflected in the total TDSS.…”

“…In light of this, we support the view that the term ''solvation/hydration dynamics'' is inappropriate for the TDSS in a protein context. 34 At the same time, the current study eliminates doubts about the picture of a heterogeneous yet overall mobile hydration layer, [1][2][3][4][5][6][7][8][9][10][11][12]18,19 which were raised by a number of previous TDSS studies. [20][21][22][23][24][25][26]…”

“…Both 17 O nuclear quadrupole relaxation (NQR) [1][2][3][4][5] experiments and multiple independent molecular dynamics (MD) simulations [6][7][8][9][10][11][12] report on a highly heterogeneous yet overall mobile hydration layer. More precisely, depending on the surface topology of the protein, few water molecules experience strong retardation, but the majority (490%) of water molecules in the first hydration shell is slowed down mildly compared to bulk water, with a retardation factor (RF) of only 2-3.…”