Double-helical structures of hyaluronan-like molecules revealed by molecular dynamics

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Double-helical structures of hyaluronan-like molecules revealed by molecular dynamics

Popis výsledku v původním jazyce

Hyaluronan, an alternating co-polymer of glucuronic acid and N-acetylglucosamine ([4)-β-D-GlcpA-(13)-β-D-GlcpNAc-(1]n) is an important biomolecule occurring in the extracellular matrix of the connective tissues, synovial fluid, vitreous fluid of eyes, etc. It has numerous biological functions, not only as a construction material, but also in signaling and regulation of biological processes. Due to its high solubility and biocompatibility it is also a promising material, especially for drug delivery systems and tissue engineering. Free macromolecules of hyaluronan in aqueous solutions form highly swollen and loosely packed random coils we studied previously using molecular dynamics[]. We have recently developed a method for modelling random coils based on molecular-dynamics (MD) simulations of 48-monosaccharides long oligosaccharides and composing the whole macromolecule from randomly chosen pieces of this fragment from different time frames of the simulation connected in accord with the statistics of the dihedral-angle couples of the glycosidic bonds []. The radii of gyration of these simulated coils are in an apparent agreement with experiment [], they follow the observed dependencies on the molecular size and concentration of salts. Furthermore, a striking similarity was found between the behavior of random coils of hyaluronan and its neutral analog containing glucose instead of glucuronic acid. This indicates that the electrostatic repulsion of carboxylate groups is not the leading force governing the random-coil shape. In the continuation of this work the detailed interactions of ions and water molecules with the macromolecules are analyzed in different electrolytes of different concentrations. Differences were found in the occurrence of different cations in the close proximity of the chain, direct interactions vs. interactions across water molecules and different affinities of different ions to different functional groups of the polymer. Especially interesting is the Ca2+ ion that interacts strongly with carboxylate groups and its influence on the macromolecule is thus rather different from other ions, e.g. Na+ and Mg2+. Finally, the effect of hydrophobic interactions was studied by simulating double-helical structures of hyaluronan, which have, however, only limited stability in water. We conclude that the random-coil shape of the hyaluronan and similar molecules is governed by its detailed interactions with ions and water molecules and cannot be accurately described only by the ionic-force based concept.

Název v anglickém jazyce

Double-helical structures of hyaluronan-like molecules revealed by molecular dynamics

Popis výsledku anglicky

Hyaluronan, an alternating co-polymer of glucuronic acid and N-acetylglucosamine ([4)-β-D-GlcpA-(13)-β-D-GlcpNAc-(1]n) is an important biomolecule occurring in the extracellular matrix of the connective tissues, synovial fluid, vitreous fluid of eyes, etc. It has numerous biological functions, not only as a construction material, but also in signaling and regulation of biological processes. Due to its high solubility and biocompatibility it is also a promising material, especially for drug delivery systems and tissue engineering. Free macromolecules of hyaluronan in aqueous solutions form highly swollen and loosely packed random coils we studied previously using molecular dynamics[]. We have recently developed a method for modelling random coils based on molecular-dynamics (MD) simulations of 48-monosaccharides long oligosaccharides and composing the whole macromolecule from randomly chosen pieces of this fragment from different time frames of the simulation connected in accord with the statistics of the dihedral-angle couples of the glycosidic bonds []. The radii of gyration of these simulated coils are in an apparent agreement with experiment [], they follow the observed dependencies on the molecular size and concentration of salts. Furthermore, a striking similarity was found between the behavior of random coils of hyaluronan and its neutral analog containing glucose instead of glucuronic acid. This indicates that the electrostatic repulsion of carboxylate groups is not the leading force governing the random-coil shape. In the continuation of this work the detailed interactions of ions and water molecules with the macromolecules are analyzed in different electrolytes of different concentrations. Differences were found in the occurrence of different cations in the close proximity of the chain, direct interactions vs. interactions across water molecules and different affinities of different ions to different functional groups of the polymer. Especially interesting is the Ca2+ ion that interacts strongly with carboxylate groups and its influence on the macromolecule is thus rather different from other ions, e.g. Na+ and Mg2+. Finally, the effect of hydrophobic interactions was studied by simulating double-helical structures of hyaluronan, which have, however, only limited stability in water. We conclude that the random-coil shape of the hyaluronan and similar molecules is governed by its detailed interactions with ions and water molecules and cannot be accurately described only by the ionic-force based concept.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10404 - Polymer science

Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů