New Insights into the Role of Water in Biological Function: Studying Solvated Biomolecules Using Terahertz Absorption Spectroscopy in Conjunction with Molecular Dynamics Simulations

Abstract

In life science, water is the ubiquitous solvent, sometimes even called the "matrix of life". There is increasing experimental and theoretical evidence that solvation water is not a passive spectator in biomolecular processes. New experimental techniques can quantify how water interacts with biomolecules and, in doing so, differs from "bulk" water. Terahertz (THz) absorption spectroscopy has turned out to be a powerful tool to study (bio)molecular hydration. The main concepts that have been developed in the recent years to describe the underlying solute-induced sub-picosecond dynamics of the hydration shell are discussed herein. Moreover, we highlight recent findings that show the significance of hydrogen bond dynamics for the function of antifreeze proteins and for molecular recognition. In all of these examples, a gradient of water motion toward functional sites of proteins is observed, the so-called "hydration funnel". By means of molecular dynamics simulations, we provide new evidence for a specific water-protein coupling as the cause of the observed dynamical heterogeneity. The efficiency of the coupling at THz frequencies is explained in terms of a two-tier (short- and long-range) solute-solvent interaction.

Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry

“…In contrast, the physical community can probe water in many different ways (Table 1). In addition to these, other potentially useful techniques include optical Kerr effect, and narrow/broad band THz/far-IR spectroscopy, 71 and more established techniques such as NMR relaxation measurements using H 2 17 O, electron spin resonance (ESR) and electron nuclear double resonance (ENDOR). En masse, these techniques have emphasized or raised many questions about the nature and implications of the related topics of 'highly structured' water, high X-ray occupancy, and water molecules of limited translational and rotational motion.…”

Perspective: Watching low-frequency vibrations of water in biomolecular recognition by THz spectroscopy

“…The low frequency modes of proteins and water can couple very effectively with a rapid energy flow between the protein and the water network modes. 1 The last years have witnessed a combined effort to develop new experimental tools in the THz range accompanied by the evolution of simulation tools for the description of the coupled solute/hydration dynamics. The information in this spectral frequency range allows an unprecedented view on the interplay of protein dynamics and hydration dynamics during molecular recognition.…”

“…1,[30][31][32] The sensitivity of the THz range to changes in hydration dynamics stems from the fact that the collective network motions of water, e.g., hydrogen bond rearrangements, translational and rotational relaxation, lie in the frequency range from 1 to 6 THz.…”

“…Directional hydrogen bonds, together with polar or charged residues, constitute a framework of non-covalent interactions within the enzyme and in the enzyme complex. 1 Water, as the generic solvent, acts as a competing agent for all these interactions, leading to a delicate balance between functional binding and complete solvation. The individual enthalpic and entropic contribution may be large.…”

Enzymatic turnover of macromolecules generates long-lasting protein–water-coupled motions beyond reaction steady state

“…However, qualitatively, we find clear significant differences for water retardation at the active site. Furthermore, when we analyzed the predicted vibrational density of states, we found that the single-stranded substrate shows an increased amount of lower energies modes as expected for a more flexible structure compared with the triple-helical substrate (34). Most importantly, we observed a correlation between the vibrational Fig.…”