An accurate coarse-grained model for chitosan polysaccharides in aqueous solution

Abstract

Computational models can provide detailed information about molecular conformations and interactions in solution, which is currently inaccessible by other means in many cases. Here we describe an efficient and precise coarse-grained model for long polysaccharides in aqueous solution at different physico-chemical conditions such as pH and ionic strength. The Model is carefully constructed based on all-atom simulations of small saccharides and metadynamics sampling of the dihedral angles in the glycosidic links, which represent the most flexible degrees of freedom of the polysaccharides. The model is validated against experimental data for Chitosan molecules in solution with various degree of deacetylation, and is shown to closely reproduce the available experimental data. For long polymers, subtle differences of the free energy maps of the glycosidic links are found to significantly affect the measurable polymer properties. Therefore, for titratable monomers the free energy maps of the corresponding links are updated according to the current charge of the monomers. We then characterize the microscopic and mesoscopic structural properties of large chitosan polysaccharides in solution for a wide range of solvent pH and ionic strength, and investigate the effect of polymer length and degree and pattern of deacetylation on the polymer properties.

A multiscale coarse-grained model to predict the molecular architecture and drug transport properties of modified chitosan hydrogels

“…To maintain predictive power in CG models, different strategies have been developed to find effective interaction potentials between CG sites, which preserve the molecular information of the material and provide a realistic representation of its large-scale behavior. CG strategies applied to polysaccharide systems include (i) parametrization to reproduce bulk thermodynamic data, 17 (ii) sampling the polymer conformations based on the conformational space available to the glycosidic angles j and c, [18][19][20] and (iii) interaction potentials that reproduce features of the atomistic system. [21][22][23][24][25][26] To date, a limited number of studies have focused on the MD simulation of chitosan-based materials.…”

“…The conformations of single chitosan chains have been explored both at atomistic 19,[27][28][29] and CG resolution. 20 Other studies have probed the properties of nanoscale aggregates at the all-atom scale. [30][31][32] Finally, the aggregation of chitosan with different w Ac and different modification patterns has been simulated with a MARTINI-like model.…”

Highly Efficient Synthesis of Type B Gelatin and Low Molecular Weight Chitosan Nanoparticles: Potential Applications as Bioactive Molecule Carriers and Cell-Penetrating Agents

“…In the case of GNPs, this behavior is most likely due to the effect of RGD (arginyl-glycyl-aspartic acid) regions present in the main backbone of, which may cause aggregation and self-assembly [ 56 ]. However, CNPs tend to form aggregates due to the ionic strength of the glucosamine units [ 57 ].…”

Systematic Structural Characterization of Chitooligosaccharides Enabled by Automated Glycan Assembly

“…However, due to the intrinsic CG approximation, chemical details are lost. In computational methods, the lack of standards to validate the theoretical models remains the major bottleneck, leading, in some cases, to contradictory theories [11b] . Well‐defined samples with controlled DP, FA, and AP are therefore important targets to shine light on molecular conformations and interaction mechanisms.…”