Hydrogen‐Bond Dynamics and Energetics of Biological Water

Abstract

Water molecules in the immediate vicinity of biomacromolecules and biomimetic organized assemblies often exhibit a markedly distinct behavior from that of their bulk counterparts. The overall sluggish behavior of biological water substantially affects the stability and integrity of biomolecules, as well as the successful execution of various crucial water‐mediated biochemical phenomena. In this Minireview, insights are provided into the features of truncated hydrogen‐bond networks that grant biological water its unique characteristics. In particular, experimental results and theoretical investigations, based on chemical kinetics, are presented that have shed light on the dynamics and energetics governing such characteristics. It is emphasized how such details help us to understand the energetics of biological water, an aspect relatively less explored than its dynamics. For instance, when biological water at hydrophilic or charged protein surfaces was explored, the free energy of H‐bond breakage was found to be of the order of 0.4 kcal mol−1 higher than that of bulk water.

Tardigrade CAHS Proteins Act as Molecular Swiss Army Knives to Mediate Desiccation Tolerance Through Multiple Mechanisms

“…[56][57][58][59][60][61] Strongly coordinated water molecules are structurally organized, have reduced motion overall and less freedom of motion, and slower exchange within hydration layers. [62][63][64][65][66][67] Therefore, faster T2 relaxation times correspond with coordinated or structured water molecules, and slower relaxations indicate less coordinated water, such as is found in bulk liquids (Fig. S5a) (see supplemental text for further details).…”

“…More dramatic water coordination is generally termed structuralization, which is characterized by strongly organized water, in which the freedom of motion of a water molecule is restricted, molecular motion is reduced, and exchange of individual water molecules of the hydration layer are reduced or slowed. [57][58][59][60][61][62] T2 (also known as spin-spin or transverse) relaxation (see supplemental text for further details) reflects the rate at which transversely magnetized nuclei decay to equilibrium, or lose coherence with one another, during the measurement period (increased relaxation kinetics; Fig. S5a).…”

The Role of Hydrogen Bonding in the Preferential Solvation of 5-Aminoquinoline in Binary Solvent Mixtures

“…The study of solvation dynamics has been an area of intense activity over the last few decades and has provided insight into solute–solvent interactions at the molecular level. This field has been enriched by rigorous theoretical calculations and simulations − on one hand and state-of-the-art spectroscopic experiments − on the other. Synergy between experiments and theory has provided deep insight into the process. , Time-dependent fluorescence Stokes shift (TDFSS) is the most popular experimental technique in this context, ,− which makes use of fluorescent probes like coumarin dyes that are significantly more dipolar in their excited state than in their ground state. , TDFSS has been used, for example, to study protein–surface interactions, biological water dynamics, and hydrogen bonding networks .…”

Interaction of the new inhibitor paxlovid (PF-07321332) and ivermectin with the monomer of the main protease SARS-CoV-2: A volumetric study based on molecular dynamics, elastic networks, classical thermodynamics and SPT

“…A common approach was the repurposing of approved pharmaceutical drugs to reduce costs, risks and time to approval/adoption in clinical settings. Computational methods with a biophysical approach can be used to discover different interactions and relevant drug phenomena that are not considered and are not found during the clinical trial process, especially for existing drugs that could offer a broader medical scope such as ivermectin ( Adhikari et al, 2020 , Aggarwal and Biswas, 2020 ).…”

“…Ivermectin has shown a higher binding energy to different target proteins of SARS-CoV-2 compared to other antiviral drugs and new candidates, such the alphaketoamide type inhibitor 13b ( González-Paz et al, 2021 ). Many proteins have been suggested to interact with ivermectin, such as the M pro protease which is responsible for most of the post-translational modifications of SARS-CoV-2 polypeptides ( Adhikari et al, 2020 , Aggarwal and Biswas, 2020 , Aghdam et al, 2021 , Agrawal et al, 2019 ). Despite all the efforts made to demonstrate the structural and energetic changes induced in M pro by the binding of ivermectin ( González-Paz et al, 2021 ), the thermodynamic changes that accompany this process from a volumetric perspective still remain unknown.…”