Quantum molecular modeling of hyaluronan

Moulabbi, M.; Broch, Henri; Robert, L.; Vasilescu, D.

doi:10.1016/s0166-1280(97)00021-3

Cited by 25 publications

(17 citation statements)

References 14 publications

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“…Crystallographic and NMR studies have concluded that D-glucose, D-galactose, and simple derivatives thereof adopt 4 C 1 chairs, 53,54 although atypical transitions from this geometry have been observed (e.g., following polysaccharide elongation). 55 This agrees with computational studies, which estimate that the 4 C 1 chair of D-glucose has a free energy 10 kcal/mol lower than the 1 C 4 chair.…”

Section: Comparison Of Computed and Experimental Monosaccharide Geometrymentioning

confidence: 99%

Less is more when simulating unsulfated glycosaminoglycan 3D‐structure: Comparison of GLYCAM06/TIP3P, PM3‐CARB1/TIP3P, and SCC‐DFTB‐D/TIP3P predictions with experiment

Sattelle¹,

Almond²

2010

J Comput Chem

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The 3D-structure of extracellular matrix glycosaminoglycans is central to function, but is currently poorly understood. Resolving this will provide insight into their heterogeneous biological roles and help to realize their significant therapeutic potential. Glycosaminoglycan chemical isoforms are too numerous to study experimentally and simulation provides a tractable alternative. However, best practice for accurate calculation of glycosaminoglycan 3D-structure within biologically relevant nanosecond timescales is uncertain. Here, we evaluate the ability of three potentials to reproduce experimentally observed glycosaminoglycan monosaccharide puckering, disaccharide 3D-conformation, and characteristic solvent interactions. Temporal dynamics of unsulfated chondroitin, chondroitin-4-sulfate, and hyaluronan β(1→3) disaccharides were simulated within TIP3P explicit solvent unrestrained for 20 ns using the GLYCAM06 force-field and two semi-empirical quantum mechanics methods, PM3-CARB1 and SCC-DFTB-D (both within a hybrid QM/MM formalism). Comparison of calculated and experimental properties (vicinal couplings, nuclear Overhauser enhancements, and glycosidic linkage geometries) showed that the carbohydrate-specific parameterization of PM3-CARB1 imparted quantifiable benefits on monosaccharide puckering and that the SCC-DFTB-D method (including an empirical correction for dispersion) best modeled the effects of hexosamine 4-sulfation. However, paradoxically, the most approximate approach (GLYCAM06/TIP3P) was the best at predicting monosaccharide puckering, 3D-conformation, and solvent interactions. Our data contribute to the debate and emerging consensus on the relative performance of these levels of theory for biological molecules.

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Section: Comparison Of Computed and Experimental Monosaccharide Geometrymentioning

confidence: 99%

Less is more when simulating unsulfated glycosaminoglycan 3D‐structure: Comparison of GLYCAM06/TIP3P, PM3‐CARB1/TIP3P, and SCC‐DFTB‐D/TIP3P predictions with experiment

Sattelle¹,

Almond²

2010

J Comput Chem

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“…Quantum chemical calculations on hyaluronan and related substances commenced in the late 1990s and represent another promising approach to uncovering the structural peculiarities of these systems. Semi-empirical [102] and low-level ab initio calculations [103] have been performed on the basic units initially. This limitation toward larger systems was also beneficial because these calculations turned attention to such local structural features that the molecular dynamics simulations aimed at large systems could not investigate in detail.…”

Section: Combined Studiesmentioning

confidence: 99%

Molecular structure of hyaluronan: an introduction

Hargittai

2008

Struct Chem

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Hyaluronan is an unbranched polysaccharide of repeating disaccharides consisting of D-glucuronic acid and N-acetyl-D-glucosamine. Its strong water-retaining ability and visco-elastic properties have been broadly utilized in medical applications. Hyaluronan is an important constituent of the extracellular matrix whose physiological functions are manifested both as the substance is by itself as well as when it is being linked to various proteins. Compared with other biopolymers, such as nucleic acids and proteins, the structural chemistry of hyaluronan is much less developed. The scarce information about the metrical aspects of its structure shows no unusual features. Its secondary structure is characterized by intramolecular hydrogen bonding that is hard to distinguish from hydrogen bonding involving water molecules when hyaluronan is in aqueous medium. The tertiary structure of hyaluronan is sensitively dependent on its environment. The relative rigidity of the glycosidic bond and the intramolecular hydrogen bonds would tend to restrict rotational freedom and thus conformational variability. This, however, seems to be overwritten by the impact of molecular environment leading to a great variability of tertiary structure. A large number of conformations are possible and may be present as witnessed by their rather small free energy differences.Of the plethora of physical techniques and computational methods, X-ray crystallography and molecular dynamics calculations have proved to be the most fruitful so far. There are untapped possibilities in NMR spectroscopy for structural studies and quantum chemical calculations are also expected to contribute substantially to the structural chemistry of hyaluronan. There are many basic data as well as structural intricacies of hyaluronan that have so far eluded the researchers of its molecular structure.

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“…Its anionic charge under physiological conditions is caused by GCU COO -, which M z+ interaction contributes to global supramolecular structure [6]. Other factors include: pH, temperature, hydration and, especially, M z+ [7,8].…”

Section: ) Consisting Of Repeating Units Of Disaccharide D-glucuronicmentioning

confidence: 99%

Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle

Torrens

Castellano

2015

ADMET DMPK

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Quantum molecular modeling of hyaluronan

Cited by 25 publications

References 14 publications

Less is more when simulating unsulfated glycosaminoglycan 3D‐structure: Comparison of GLYCAM06/TIP3P, PM3‐CARB1/TIP3P, and SCC‐DFTB‐D/TIP3P predictions with experiment

Less is more when simulating unsulfated glycosaminoglycan 3D‐structure: Comparison of GLYCAM06/TIP3P, PM3‐CARB1/TIP3P, and SCC‐DFTB‐D/TIP3P predictions with experiment

Molecular structure of hyaluronan: an introduction

Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle

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