The spatial range of protein hydration

Abstract

Proteins interact with their aqueous surroundings, thereby modifying the physical properties of the solvent. The extent of this perturbation has been investigated by numerous methods in the past half-century, but a consensus has still not emerged regarding the spatial range of the perturbation. To a large extent, the disparate views found in the current literature can be traced to the lack of a rigorous definition of the perturbation range. Stating that a particular solvent property differs from its bulk value at a certain distance from the protein is not particularly helpful since such findings depend on the sensitivity and precision of the technique used to probe the system. What is needed is a well-defined decay length, an intrinsic property of the protein in a dilute aqueous solution, that specifies the length scale on which a given physical property approaches its bulk-water value. Based on molecular dynamics simulations of four small globular proteins, we present such an analysis of the structural and dynamic properties of the hydrogen-bonded solvent network. The results demonstrate unequivocally that the solvent perturbation is short-ranged, with all investigated properties having exponential decay lengths of less than one hydration shell. The short range of the perturbation is a consequence of the high energy density of bulk water, rendering this solvent highly resistant to structural perturbations. The electric field from the protein, which under certain conditions can be long-ranged, induces a weak alignment of water dipoles, which, however, is merely the linear dielectric response of bulk water and, therefore, should not be thought of as a structural perturbation. By decomposing the first hydration shell into polarity-based subsets, we find that the hydration structure of the nonpolar parts of the protein surface is similar to that of small nonpolar solutes. For all four examined proteins, the mean number of water-water hydrogen bonds in the nonpolar subset is within 1% of the value in bulk water, suggesting that the fragmentation and topography of the nonpolar protein-water interface has evolved to minimize the propensity for protein aggregation by reducing the unfavorable free energy of hydrophobic hydration.

Polycation–Anionic Lipid Membrane Interactions

“…We also calculated the radial orientation of the water molecules around the oligomers in systems M20-1, M20-2, and M40-1 ( Figure S9 ) by considering each unit in each polycation chain independently and computing the dipolar alignment order parameters 35 as a function of the distance from the center of mass of the corresponding PMAPTAC unit. After averaging the calculated order parameters for each system, we observed a preferential orientation of water molecules around the PMAPTAC oligomer within 5 nm from the polymer chain, which is unaffected by the presence of KCl.…”

Solvation Layer of Antifreeze Proteins Analyzed with a Markov State Model

“…It is the interplay between water and protein that determines the properties of the latter to a large extent, a problem that has been studied since decades 89 and still is a matter of intense research. 90…”

The Molecular Interaction Process

“…46 However, more recent, definitive work indicates there is good justification for including only the first solvent layer. [47][48][49][50][51][52] If we consider the potential energies that stabilize the conformation of the molecule, they will include the energetics within the van der Waals boundary of the protein, as well as those between the van der Waal's surface and this first solvent layer. These energies describe the influences on molecular characteristics, such as resistance to melting/denaturing and structural flexibility.…”

“…[77][78][79] A wide array of methods indicate that surface waters form a layer~3 Å thick and with a density that is~10%-15% greater than bulk water. 47,51 The surface water should not be confused with the water that contributes to the hydrodynamic radius, which NMR methods suggest is closer to 0.3 water layers thick. 51 Magnetic resonance dispersion analysis using 17 O indicates that all surface waters are highly dynamic, exchanging readily with bulk solvent and having a rotational diffusion coefficient close to that of bulk water.…”

“…47,51 The surface water should not be confused with the water that contributes to the hydrodynamic radius, which NMR methods suggest is closer to 0.3 water layers thick. 51 Magnetic resonance dispersion analysis using 17 O indicates that all surface waters are highly dynamic, exchanging readily with bulk solvent and having a rotational diffusion coefficient close to that of bulk water. 47,52 However, being dynamic is not the same as being removed, and for the surfaces to touch, the water must be removed.…”