Sensitivity of polarization fluctuations to the nature of protein-water interactions: Study of biological water in four different protein-water systems

Abstract

Since the time of Kirkwood, observed deviations in magnitude of the dielectric constant of aqueous protein solution from that of neat water (∼80) and slower decay of polarization have been subjects of enormous interest, controversy, and debate. Most of the common proteins have large permanent dipole moments (often more than 100 D) that can influence structure and dynamics of even distant water molecules, thereby affecting collective polarization fluctuation of the solution, which in turn can significantly alter solution's dielectric constant. Therefore, distance dependence of polarization fluctuation can provide important insight into the nature of biological water. We explore these aspects by studying aqueous solutions of four different proteins of different characteristics and varying sizes, chicken villin headpiece subdomain (HP-36), immunoglobulin binding domain protein G (GB1), hen-egg white lysozyme (LYS), and Myoglobin (MYO). We simulate fairly large systems consisting of single protein molecule and 20000-30000 water molecules (varied according to the protein size), providing a concentration in the range of ∼2-3 mM. We find that the calculated dielectric constant of the system shows a noticeable increment in all the cases compared to that of neat water. Total dipole moment auto time correlation function of water ⟨δMW(0)δMW(t)⟩ is found to be sensitive to the nature of the protein. Surprisingly, dipole moment of the protein and total dipole moment of the water molecules are found to be only weakly coupled. Shellwise decomposition of water molecules around protein reveals higher density of first layer compared to the succeeding ones. We also calculate heuristic effective dielectric constant of successive layers and find that the layer adjacent to protein has much lower value (∼50). However, progressive layers exhibit successive increment of dielectric constant, finally reaching a value close to that of bulk 4-5 layers away. We also calculate shellwise orientational correlation function and tetrahedral order parameter to understand the local dynamics and structural re-arrangement of water. Theoretical analysis providing simple method for calculation of shellwise local dielectric constant and implication of these findings are elaborately discussed in the present work.

Hydrogen Bond Network of Water around Protein Investigated with Terahertz and Infrared Spectroscopy

“…From the THz to FIR region (0.25~12 THz), where we revealed the contribution of dissolved albumin solute is negligibly small, the hydration state and the water HB structure were analyzed. First, by defining hydration water as those water molecules that exhibit dynamically retarded reorientation compared with bulk water, we found z 3500 hydration water molecules corresponding to a layer of water molecules extending z 8.5 Å (three to four water layers) out from the protein surface, in good agreement with recent MD simulation studies (21,22). Second, the water HB structure around albumin is discussed in terms of HB fragmentation (the population of NHB water) and the distortion of the HB network.…”

“…In contrast, by defining reorientationally retarded water as hydration water in our study, we found three to four water layers (~8.5 Å ) from the albumin surface exhibit water dynamics that distinguish it from that of bulk water. This ''global hydration'' view (21,22,(39)(40)(41)(42)(43)(44) is consistent with recent MD simulations, where the perturbation of water's orientational structure induced by the protein was found to be long-ranged, propagating out to three to five hydration shells (21,22).…”

“…5) in albumin aqueous solution masks the variation of the ''aggregated'' g S , but we can assert the damping constant of hydration water is qualitatively larger than that of bulk water. Since the damping constant g S represents the degree of heterogeneity of the HB environment, large g S of hydration water compared with that of bulk claims that hydration water has a heterogeneous HB network structure, which consists of various HB distances and angles, in good accordance with previous experiments (26,35,37) and simulations (12,14,21,96,97). Such heterogeneous HBs are associated with the distortion of the water HB network, since they involve the distortion of the O...O...O angles from the ideal tetrahedral value.…”

“…The reason for this distorted HB structure around protein is that the protein surface, which is topologically and energetically heterogeneous, is structurally incompatible with the tetrahedral-like HB network of bulk water (16)(17)(18)(19)(20). Considering a distorted tetrahedral structure generally increases water density (98), the small compressibility (2) and the~5% to 10% higher density (12,21,23) of water in the first hydration shell of protein are closely associated with the structural distortion of the water HB network that stems from topological and energetic disorder of the protein surface. In addition, since such a distorted structure of hydration water is not compatible with freezable water (i.e., regular tetrahedral coordination), the structural distortion imposed by protein is thought to be an origin of nonfreezing characteristics (1) of hydration water.…”

“…Molecular dynamics (MD) simulations (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) and other experimental approaches (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) have revealed the protein is surrounded by dynamically retarded hydration water, with the innermost shell having a density higher than that of bulk water. However, even today, experimentally characterizing the dynamics and the structure of the water HB network in this hydration shell is challenging, because the water-water HB lifetime is very short (typically 1 ps) (38).…”