The geometry of protein hydration

Abstract

Based on molecular dynamics simulations of four globular proteins in dilute aqueous solution, with three different water models, we examine several, essentially geometrical, aspects of the protein-water interface that remain controversial or incompletely understood. First, we compare different hydration shell definitions, based on spatial or topological proximity criteria. We find that the best method for constructing monolayer shells with nearly complete coverage is to use a 5 Å water-carbon cutoff and a 4 Å water-water cutoff. Using this method, we determine a mean interfacial water area of 11.1 Å which appears to be a universal property of the protein-water interface. We then analyze the local coordination and packing density of water molecules in the hydration shells and in subsets of the first shell. The mean polar water coordination number in the first shell remains within 1% of the bulk-water value, and it is 5% lower in the nonpolar part of the first shell. The local packing density is obtained from additively weighted Voronoi tessellation, arguably the most physically realistic method for allocating space between protein and water. We find that water in all parts of the first hydration shell, including the nonpolar part, is more densely packed than in the bulk, with a shell-averaged density excess of 6% for all four proteins. We suggest reasons why this value differs from previous experimental and computational results, emphasizing the importance of a realistic placement of the protein-water dividing surface and the distinction between spatial correlation and packing density. The protein-induced perturbation of water coordination and packing density is found to be short-ranged, with an exponential decay "length" of 0.6 shells. We also compute the protein partial volume, analyze its decomposition, and argue against the relevance of electrostriction.

Structure and Dynamics of the Central Lipid Pool and Proteins of the Bacterial Holo-Translocon

“…A combination of the home-written software CaPP (v. 3.9; github.com/Niels-Bohr-Institute-XNS-StructBiophys/CaPP) and WillItFit ( 18 ) were used to fit the data. A 3 Å thick water layer with 6% higher scattering length than bulk D 2 O was added ( 19 ) but was excluded from the hydrophobic transmembrane region. The thickness of this was set to 30.6 Å in accordance with the hydrophobic bilayer thickness reported in the orientations of proteins in membranes database ( 20 ).…”

Length-scale dependence of protein hydration-shell density

“…The hydration of bio-molecular systems plays important roles in their stability, 1 dynamics, [2][3][4] folding, 5 ligand recognition 6,7 and function. 8,9 There have been a variety of theoretical [9][10][11][12][13][14][15][16][17][18] and experimental 3,[19][20][21][22][23][24][25][26][27][28][29][30][31][32] studies demonstrating that proteins modify the structural and dynamical organization of their surrounding water molecules. The thickness of protein hydration shells inferred from most studies is in the range of 1-1.2 nm, [13][14][15]18,33 although larger, long-ranged dynamical solvation shells have been hypothesized on the basis of terahertz spectroscopical studies.…”

“…The thickness of protein hydration shells inferred from most studies is in the range of 1-1.2 nm, [13][14][15]18,33 although larger, long-ranged dynamical solvation shells have been hypothesized on the basis of terahertz spectroscopical studies. 25,34,35 Although it is now rather well accepted that the density of the protein hydration shell is higher than the bulk one, 11,12,15,16,18,20 there is not a consensus about the magnitude of this increment. Depending on the protein, on the experimental technique, or on the computational approach, used and on the distance from the protein surface at which the density increment is evaluated, different estimates have been given ranging from 1% to 50%.…”

“…Depending on the protein, on the experimental technique, or on the computational approach, used and on the distance from the protein surface at which the density increment is evaluated, different estimates have been given ranging from 1% to 50%. 11,12,16,20 Here, we focus on the dependence of the protein hydration shell density on the protein size, and partly function by analyzing the hydration properties of eighteen different proteins, out of which eight are antifreeze proteins (AFPs), by means of MD simulation and a recently developed analysis to investigate hydration shell densities. 15,18 Previous work have focused on the length-scale dependence of the hydration density of hydrophobic solutes [36][37][38][39] but, to the best of our knowledge, this is the first systematic analysis of the correlation between hydration shell densities and the size and shape of globular proteins, which are systems with amphipathic surfaces.…”

Different force fields give rise to different amyloid aggregation pathways in molecular dynamics simulations

“…However, the interfacial water area (IWA), which is the ratio of the SASA to the number of waters within the first hydration shell, attains an almost constant value of IWA = 0.096 nm 2 for all peptides and force fields. For globular proteins an IWA value of 0.11 nm 2 has been previously reported 68 suggesting that Aβ 16−22 has a higher solvent density than the globular proteins. Figure 3: The average number of H-bonds formed between wt residues and water.…”