Hyaluronan random coils in electrolyte solutions—a molecular dynamics study

A computational method of modeling random coils of hyaluronan was developed based on the molecular-dynamics simulations. An oligosaccharide of 48 monosaccharide units was equilibrated within a 70–100 ns simulation and randomly chosen pieces of this molecule from different simulation frames were combined to constitute a long polysaccharide chain, both for hyaluronan and its non-ionic analog containing glucose instead of glucuronic acid. The dihedral angles of the glycoside connections of the pieces obeyed the statistics deduced from the simulation. The simulations were performed at various concentrations of NaCl and MgCl2. The calculated radii of gyration show a striking agreement with experimental data from the literature and indicate a key importance of the polymer-ion interactions for the random-coil conformation, but a low influence of the excluded volume of the chain and the carboxylate-groups repulsion. The method has thus the potential to become a versatile tool of modeling macromolecules of various semirigid polymers. © 2017 Elsevier LtdNational Grid Infrastructure MetaCentrum, provided under the program "Projects of Large Research, Development, and Innovations Infrastructures" [CESNET LM2015042

Equilibria of oligomeric proteins under high pressure – A theoretical description

High pressure methods have become a useful tool for studying protein structure and stability. Using them, various physico-chemical processes including protein unfolding, aggregation, oligomer dissociation or enzyme-activity decrease were studied on many different proteins. Oligomeric protein dissociation is a process that can perfectly utilize the potential of high-pressure techniques, as the high pressure shifts the equilibria to higher concentrations making them better observable by spectroscopic methods. This can be especially useful when the oligomeric form is highly stable at atmospheric pressure. These applications may be, however, hindered by less intensive experimental response as well as interference of the oligomerization equilibria with unfolding or aggregation of the subunits, but also by more complex theoretical description. In this study we develop mathematical models describing different kinds of oligomerization equilibria, both closed (equilibrium of monomer and the highest possible oligomer without any intermediates) and consecutive. Closed homooligomer equilibria are discussed for any oligomerization degree, while the more complex heterooligomer equilibria and the consecutive equilibria in both homo- and heterooligomers are taken into account only for dimers and trimers. In all the cases, fractions of all the relevant forms are evaluated as functions of pressure and concentration. Significant points (inflection points and extremes) of the resulting transition curves, that can be determined experimentally, are evaluated as functions of pressure and/or concentration. These functions can be further used in order to evaluate the thermodynamic parameters of the system, i.e. atmospheric-pressure equilibrium constants and volume changes of the individual steps of the oligomer-dissociation processes. © 2016 Elsevier LtdP208-12-G016, GACR, Grant Agency of the Czech RepublicGrant Agency of the Czech Republic [P208-12-G016

Pressure induced structural changes and dimer destabilization of HIV-1 protease studied by molecular dynamics simulations

High-pressure methods have become attractive tools for investigation of the structural stability of proteins. Besides protein unfolding, dimerization can be studied this way, too. HIV-1 protease is a convenient target of experimental and theoretical high-pressure studies. In this study molecular-dynamics simulations are used to predict the response of HIV-1 protease to the pressure of 0.1 to 600 MPa. The protease conformation of both the monomer and the dimer is highly rigid changing insignificantly with growing pressure. Hydrophobicity of the protease decreases with increasing pressure. Water density inside the active-site cavity grows from 87% to 100% of the bulk water density within the pressure range. The dimer-dissociation volume change is negative for most of the pressure ranges with the minimum of -105 ml mol-1, except for a short interval of positive values at low pressures. The dimer is thus slightly stabilized up to 160 MPa, but strongly destabilized by higher pressures.P41-RR005969, NIH, National Institutes of HealthNational Institutes of Health [P41-RR005969

A novel hydrogel based on renewable materials for agricultural application

This study details the design and characterization of a new, biodegradable, and renewable whey/cellulose-based hydrogel (i.e., agricultural hydrogel). This was formulated from cellulose derivatives (carboxymethylcellulose (CMC) and hydroxyethylcellulose (HEC)) and acid whey cross-linked with citric acid, with the aim to obtain an agricultural product with a high swelling capacity to uphold the quality of soil and conserve water resources. With regard to the swelling behaviour of the prepared hydrogels, the authors initially assessed the swelling ratio and capacity for water uptake. Evaluating the chemical structure of the hydrogel and its thermal and viscoelastic properties involved performing Fourier transform infrared spectroscopy, differential scanning colorimetry, thermal gravimetric analysis, and rheological measurement of the hydrogel films. According to preliminary results, sufficient swelling capacity and stiffness were observed in a hydrogel prepared with 3% CMC and HEC, cross-linked with 5% citric acid. Moreover, the kinetics of water uptake revealed a promising capacity that was sustainable after 5 drying and swelling cycles. The results confirmed that the stability of the hydrogel was enhanced by the presence of the citric acid. As a consequence, it is necessary to utilize an appropriate cross-linking concentration and abide by certain conditions to ensure the swelling properties of the prepared hydrogel are sufficient. Further investigation of the topic, especially in relation to applications in soil, could confirm if the whey-cellulose-based hydrogel is actually suitable for agricultural use, thereby contributing to the advancement of sustainable arable farming. © 2020 Silvie Durpekova et al.Ministry of Agriculture of the Czech RepublicMinistry of Agriculture, Czech Republic [QK1910392]; Czech Ministry of Education, Youth and SportsMinistry of Education, Youth & Sports - Czech Republic [LO1504

Magnetorheological elastomers: Electric properties versus microstructure

A series of composite materials comprising elastomeric matrix filled with magnetic filler (magnetorheological elastomer) were prepared in two morphological variants, namely with random and organized spatial distribution of filler particles. Orderly arrangement in the latter case was achieved through application of magnetic field throughout curing. Influence of filler concentration and its arrangement in magnetorheological elastomers (isotropic and anisotropic) on electric properties was studied by the means of dc conductivity measurement and dielectric relaxation spectroscopy. Qualitatively different behavior was observed for anisotropic samples with relaxations linked to charge transport along filler clusters. Activation energy of these was extracted from temperature measurements and found to decrease with filler loading as inter-particle distance diminishes. Strongly non-linear character of this decrease was explained by decreasing degree of anisotropy in structured samples with increasing filler loading due to spatial and viscous effects preventing arrangement of filler as regular as in case of low concentrations. This correlation, i.e. between dielectric properties and inner structure of magnetorheological elastomers, is employed for description of such systems inner morphology. © 2018 Author(s).Czech Science Foundation [17-24730S]Czech Science FoundationGrant Agency of the Czech Republic [17-24730S

Hyaluronan oligosaccharides form double-helical duplexes in water:1,4-dioxane mixed solvent

Hyaluronic acid (HA) is a hydrophilic natural polysaccharide consisting of alternating monosaccharide units of glucuronic acid and N-acetyl glucosamine. In aqueous solutions the electrostatic repulsion of the carboxylate groups hampers the formation of supermolecular structures that can be partially stabilized by the addition of salt. Increased permittivity of the mixed water:organic solvents causes better compensation of the negative charge of HA chains by dissolved cations which changes their interactions with other molecules. In this study we simulate interactions of two HA chains in water:1,4-dioxane and water:tert-butanol mixed solvents with varying NaCl concentrations using molecular dynamics (MD). Anti-parallel double-helix-like duplexes are formed in NaCl-containing water:1,4-dioxane mixture and remain stable even when NaCl is removed. Parallel duplexes separate after a short time. In water:tert-butanol analogous duplexes are unstable. Stability of HA duplexes is thus determined by the solvent composition and the ability of its components to separate in the solvation shell of HA molecules, as well as by the mutual orientation of the chains.Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT, (90254); Univerzita Tomáše Bati ve Zlíně, UTB, (IGA/FT/2022/009, IGA/FT/2023/006)Ministry of Education, Youth and Sports of the Czech Republic through e-INFRA CZ [90254]; Internal funding agency of Tomas Bata University in Zlin [IGA/FT/2022/009, IGA/FT/2023/006

Effect of solvent and ions on the structure and dynamics of a hyaluronan molecule

Hyaluronic acid (hyaluronan, HA) is a negatively charged polysaccharide forming highly swollen random coils in aqueous solutions. Their size decreases along with growing salt concentration, but the mechanism of this phenomenon remains unclear. We carry out molecular-dynamics simulations of a 48-monosaccharide HA oligomer in varying salt concentration and temperature. They identify the interaction points of Na+ ions with the HA chain and reveal their influence on the HA solvation-shell structure. The salt-dependent variation of the molecular size does not consist in the distribution of the dihedral angles of the glycosidic connections but is driven by the random flips of individual dihedral angles, which cause the formation of temporary hairpin-like structures effectively shortening the chain. They are induced by the frequency of cation-chain interactions that grow with the salt concentration, but is reduced by the simultaneous decrease of ions’ activities. This leads to an anomalous random-coil shrinkage at 0.6 M salt concentration. © 2020 The AuthorsInternal Funding Agency of Tomas Bata University in Zlin [IGA/FT/2016/011, IGA/FT/2017/009, IGA/FT/2018/010]; Grant Agency of the Czech RepublicGrant Agency of the Czech Republic [P208-12-G016

Salt-dependent intermolecular interactions of hyaluronan molecules mediate the formation of temporary duplex structures

Hyaluronic acid (HA) is a natural polysaccharide present in the connective tissues of vertebrates, often used in the cosmetics and pharmaceutical industries. HA is a strongly hydrophilic macromolecule forming highly swollen random coils in aqueous solutions. Although some authors reported the secondary and tertiary structures of HA chain, others brought convincing evidence contradicting this hypothesis. This study aims at investigation of the stability and dynamics of the temporary duplex HA structures at different NaCl concentrations by molecular-dynamics (MD) simulations. The tendency to duplex formation grows with NaCl concentration reaching its maximum at 0.6 M. This profile is a result of two counteracting NaCl-concentration dependent phenomena, the growing electrostatic-repulsion screening on one side and the disturbance of hydrogen-bonds formation on the other side. Although the weak intermolecular attraction cannot lead to long-lived secondary and tertiary structures, it may influence the properties of large HA macromolecules and concentrated HA solutions. © 2022 Elsevier LtdMinisterstvo Školství, Mládeže a Tělovýchovy, MŠMT: 90140; Univerzita Tomáše Bati ve Zlíně: IGA/FT/2016/011, IGA/FT/2017/009, IGA/FT/2018/010, IGA/FT/2021/010, IGA/FT/2022/00