Terahertz Spectral Domain Computational Analysis of Hydration Shell of Proteins with Increasingly Complex Tertiary Structure

Abstract

Solvation dynamics of biomolecules and water in a hydration shell have been studied by different methods; however, a clear picture of this process is not yet established. Terahertz (THz) studies of molecular behavior in binary solutions present unique information on the picosecond motions of molecules. A complete mechanical interpretation of THz absorption spectra associated with solvated biomolecules remains a challenging task. The Gromacs molecular dynamics (MD) simulation package is used here to examine the spectral characteristics of water molecules in close proximity to biomolecules using vibrational density of states (VDOS). Systematic simulation of solvation dynamics of proteins of different size and tertiary structure are presented. The following have been selected for analysis. They range from less to more complex tertiary structure (corresponding to an increased number of secondary structure elements): TRP-cage13-20 peptide, TRP-cage, BPTI, and lysozyme. The initial study predicts that the depth of the hydration shell, determined by VDOS of water, extends to approximately 10 Å and does not depend on protein size. Furthermore the integral perturbation coefficient of the whole solvation layer is found to be increased for larger proteins due to a higher retardation rate of water molecules in their shells. Differences in solvation dynamics among the proteins considered originate primarily from the water molecules buried in the interior of the protein and not from the on-surface molecules.

Sub-terahertz spectroscopy reveals that proteins influence the properties of water at greater distances than previously detected

“…Instead, the actual size of the proteins (Table I) has been used. Next, the water molecules buried in the interior of the protein 39 were not considered in the calculation of the hydration shell size, but only on-surface water molecules belonging to the hydration shell (in its conventional meaning). According to this approach, the final expression for estimation of hydration shell-size is described by…”

“…Such a depth of hydration water around proteins demonstrates that protein-water interactions are complex and extend beyond the first two to three layers of water molecules as estimated by MD simulations. 39 Via this deep hydration shell, a protein can influence the dynamics of a potential binding agent (or ligand), and possibly even capture and orient it into the required attitude for binding. This might bring new insights into molecular binding and recognition processes.…”

“…MD simulations were performed using the Gromacs package (version 4.5). Gromacs was utilized to accurately estimate (1) the number of water molecules excluded by each protein, by simulating water boxes of the same volume-one with protein, another with pure water; (2) the number of water molecules in the protein interior by the distance criterion as used by Sushko et al 39 The simulation protocol is as described by Sushko et al 39 Solutions undergo initial neutralization followed by steepest-descent energy minimization. Proteins were solvated in a TIP3P waterbox and allowed to equilibrate at 300 K before a production run of 100 ps.…”

Nanoantenna enhanced terahertz interaction of biomolecules

“…The depth of hydration shell in the hydrated lysosome, BPTI, TRP-cage, and TRP-tail was estimated using MD simulations. 218 To perform a basic MD simulation of a molecule, 236 first and foremost a force field must be applied to characterize the molecular interaction of the molecules. In the next step, the molecule is positioned in a unit cell of desired shape and size followed by the addition of water molecules, known as solvation step.…”

“…THz time-domain analysis obtained using MD simulations. (A) Velocity autocorrelation fuction (VACF) and (B) vibrational density of states of oxygen (ox) and hydrogen (h) in first solvation layer (3Å) of lysosome and bulk water.Reprinted with permission from Ref 218. .…”