How Water's Properties Are Encoded in Its Molecular Structure and Energies.

How are water's material properties encoded within the structure of the water molecule? This is pertinent to understanding Earth's living systems, its materials, its geochemistry and geophysics, and a broad spectrum of its industrial chemistry. Water has distinctive liquid and solid properties: It is highly cohesive. It has volumetric anomalies-water's solid (ice) floats on its liquid; pressure can melt the solid rather than freezing the liquid; heating can shrink the liquid. It has more solid phases than other materials. Its supercooled liquid has divergent thermodynamic response functions. Its glassy state is neither fragile nor strong. Its component ions-hydroxide and protons-diffuse much faster than other ions. Aqueous solvation of ions or oils entails large entropies and heat capacities. We review how these properties are encoded within water's molecular structure and energies, as understood from theories, simulations, and experiments. Like simpler liquids, water molecules are nearly spherical and interact with each other through van der Waals forces. Unlike simpler liquids, water's orientation-dependent hydrogen bonding leads to open tetrahedral cage-like structuring that contributes to its remarkable volumetric and thermal properties

The role of buffers in wild-type HEWL amyloid fibril formation mechanism

Amyloid fibrils, highly ordered protein aggregates, play an important role in the onset of several neurological disorders. Many studies have assessed amyloid fibril formation under specific solution conditions, but they all lack an important phenomena in biological solutions—buffer specific effects. We have focused on the formation of hen egg-white lysozyme (HEWL) fibrils in aqueous solutions of different buffers in both acidic and basic pH range. By means of UV-Vis spectroscopy, fluorescence measurements and CD spectroscopy, we have managed to show that fibrillization of HEWL is affected by buffer identity (glycine, TRIS, phosphate, KCl-HCl, cacodylate, HEPES, acetate), solution pH, sample incubation (agitated vs. static) and added excipients (NaCl and PEG). HEWL only forms amyloid fibrils at pH = 2.0 under agitated conditions in glycine and KCl-HCl buffers of high enough ionic strength. Phosphate buffer on the other hand stabilizes the HEWL molecules. Similar stabilization effect was achieved by addition of PEG12000 molecules to the solution

The influence of excipients on the viscosity of monoclonal antibody solutions

The aggregation propensity of monoclonal antibodies can be modified by adding different cosolutes into the solution. A simple coarse-grained model in the combination with the thermodynamic perturbation theory was used to predict cluster distribution and viscosity of the solutions of IgG4 monoclonal anibody in the presence of L-Arginine Hydrochloride. The data were analysed using binding polynomial to describe the binding of cosolute (Arginine) to the antibody molecule. The results show that by binding to the antibody molecule the cosolute occupies some of the binding sites of the antibody, and in this way reduces the amount of binding sites available to other antibody molecules. The aggregation propensity of the antibody molecules is therefore reduced

Applicability of a central force water model to study adsorption in disordered hydrophobic matrices - replica Ornstein-Zernike theory

A simple central force water model to study adsorption in random Lennard-Jones-like matrices has been studied using the replica Ornstein–Zernike integral equation theory in hypernetted-chain (HNC) approximation and in HNC+bridge approximation. The structure of water in obstacle matrices of different sizes was studied, showing that the model appropriately accounts for the hydrophobic hydration. By calculating the chemical potential of water in the model adsorbent, we have constructed the adsorption isotherm. Except for the cases of highly dispersed matrices, water gets excluded from the crowded hydrophobic environment, as expected experimentally

The mechanism of self-association of human ▫gammagamma▫-D crystallin from molecular dynamics simulations

The aggregation of human $delta$-D crystallin is associated with the age-onset cataract formation. Here, we extensively investigated the self-association mechanism of human $delta$-D crystallin through molecular dynamics computer simulations. By mutating the protein surface we found that electrostatic interactions between charged amino acids play a crucial role in its self-association. We have confirmed the two-fold role of arginine molecules. If they are located as residues on the protein surface they can initiate protein contacts and contribute to their stickiness with noteworthy hydrophobic interactions through stacking of their methylene groups. But if they are added as free arginine in the protein solution they can also stabilize it, by associating with the protein surface and also with themselves to form effective inter-protein spacers that obstruct protein aggregation

The Effect of Arginine on the Phase Stability of Aqueous Hen Egg-White Lysozyme Solutions

The effect of arginine on the phase stability of the hen egg-white lysozyme (HEWL) has been studied via molecular dynamics computer simulations, as well as experimentally via cloud-point temperature determination. The experiments show that the addition of arginine increases the stability of the HEWL solutions. The computer simulation results indicate that arginine molecules tend to self-associate. If arginine residues are located on the protein surface, the free arginine molecules stay in their vicinity and prevent the way protein molecules “connect” through them to form clusters. The results are not sensitive to a particular force field and suggest a possible microscopic mechanism of the stabilizing role of arginine as an excipient

The Role of Buffers in Wild-Type HEWL Amyloid Fibril Formation Mechanism

Amyloid fibrils, highly ordered protein aggregates, play an important role in the onset of several neurological disorders. Many studies have assessed amyloid fibril formation under specific solution conditions, but they all lack an important phenomena in biological solutions—buffer specific effects. We have focused on the formation of hen egg-white lysozyme (HEWL) fibrils in aqueous solutions of different buffers in both acidic and basic pH range. By means of UV-Vis spectroscopy, fluorescence measurements and CD spectroscopy, we have managed to show that fibrillization of HEWL is affected by buffer identity (glycine, TRIS, phosphate, KCl-HCl, cacodylate, HEPES, acetate), solution pH, sample incubation (agitated vs. static) and added excipients (NaCl and PEG). HEWL only forms amyloid fibrils at pH = 2.0 under agitated conditions in glycine and KCl-HCl buffers of high enough ionic strength. Phosphate buffer on the other hand stabilizes the HEWL molecules. Similar stabilization effect was achieved by addition of PEG12000 molecules to the solution

On thermodynamics and mobility of ions enclosed within charged nanoporous system

New simulations and integral equation results are presented for a model partly quenched system composed of monovalent ions. Static and dynamic properties of the system are explored using the replica Ornstein–Zernike theory in the hypernetted chain approximation and Brownian dynamic simulations. The model system consists of two subsystems: one is a collection of charged obstacles (matrix), and the other is an invading electrolyte. The overall system is electroneutral, while the subsystems are not. Charged species are represented by Lennard–Jones spheres of equal size, with either positive or negative charge in the center. The solvent is treated as a continuous dielectric. The purpose of this study is to correlate the mobility of ions (self-diffusion coefficients) with their individual activity coefficients. In addition, the effects of the matrix preparation and of the conditions of observation (dielectric constant of solvent, temperature) are investigated. For the first time, the effect of the charged obstacles on the excess internal energy of the electrolyte solution is also examined

A new fibrillization mechanism of ß-lactoglobulin in glycine solutions

Even though amyloid aggregates were discovered many years ago the mechanism of their formation is still a mystery. Because of their connection to many of untreatable neurodegenerative diseases the motivation for finding a common aggregation path is high. We report a new high heat induced fibrillization path of a model protein β-lactoglobulin (BLG) when incubated in glycine instead of water at pH 2. By combining atomic force microscopy (AFM), transmission emission microscopy (TEM), dynamic light scattering (DLS) and circular dichroism (CD) we predict that the basic building blocks of fibrils made in glycine are not peptides, but rather spheroid oligomers of different height that form by stacking of ring-like structures. Spheroid oligomers linearly align to form fibrils by opening up and combining. We suspect that glycine acts as an hydrolysation inhibitor which consequently promotes a different fibrillization path. By combining the known data on fibrillization in water with our experimental conclusions we come up with a new fibrillization scheme for BLG. We show that by changing the fibrillization conditions just by small changes in buffer composition can dramatically change the aggregation pathway and the effect of buffer shouldn\u27t be neglected. Fibrils seen in our study are also gaining more and more attention because of their pore-like structure and a possible cytotoxic mechanism by forming pernicious ion-channels. By preparing them in a simple model system as BLG we opened a new way to study their formation