Water Determines the Structure and Dynamics of Proteins

Abstract

Water is an essential participant in the stability, structure, dynamics, and function of proteins and other biomolecules. Thermodynamically, changes in the aqueous environment affect the stability of biomolecules. Structurally, water participates chemically in the catalytic function of proteins and nucleic acids and physically in the collapse of the protein chain during folding through hydrophobic collapse and mediates binding through the hydrogen bond in complex formation. Water is a partner that slaves the dynamics of proteins, and water interaction with proteins affect their dynamics. Here we provide a review of the experimental and computational advances over the past decade in understanding the role of water in the dynamics, structure, and function of proteins. We focus on the combination of X-ray and neutron crystallography, NMR, terahertz spectroscopy, mass spectroscopy, thermodynamics, and computer simulations to reveal how water assist proteins in their function. The recent advances in computer simulations and the enhanced sensitivity of experimental tools promise major advances in the understanding of protein dynamics, and water surely will be a protagonist.

Structural basis for the dissociation of α-synuclein fibrils triggered by pressure perturbation of the hydrophobic core

“…6). Indeed, the hydration of exposed nonpolar residues, the presence of non-exposed cavities, and the electrostriction of exposed charges are key elements in explaining protein unfolding triggered by pressure20323334. The recent ssNMR structure of the Greek-key α-syn fibril provided the framework for understanding fibril stability31 and insights into how pressure would affect its core (Fig.…”

“…The recently published structure of a toxic α-syn fibril reveals a structural topology consisting of a Greek-key motif with multiple β-strands intercalated with steric zippers, generating a compact, hydrophobic core31 that may explain why these fibrils are sensitive to pressure2324. The folding of proteins into globular or fibrillar states is based on the formation of water-excluded cavities that can be perturbed by pressure20323334.…”

Role of the hydrophobic and hydrophilic sites in the dynamic crossover of the protein-hydration water

“…In most cases instead of being just an involving layer which increases the solubility, hydration water is an active participant in the dynamics of these molecules [1]. Then, the water first layer and the biomolecule should not be considered as separated entities but form a biologically active entity [2].…”

Comment on “Enhanced water permeability and tunable ion selectivity in subnanometer carbon nanotube porins”

“…Equilibration between the individual jumps is ensured by the short hydrogen bond lifetime, which is~2 ps in neat water. A much longer lifetime for pore waters (as sometimes observed for waters of hydration) seems doubtful because they retain bulk diffusibility (6). The theory of water permeation through nanotubes describes an analogous situation with imaginary water-binding sites (4).…”