Overcoming the Limitations of the MARTINI Force Field in Simulations of Polysaccharides

Polysaccharides (carbohydrates) are key regulators of a large number of cell biological processes. However, precise biochemical or genetic manipulation of these often complex structures is laborious and hampers experimental structure–function studies. Molecular Dynamics (MD) simulations provide a va...

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Bibliographic Details
Published in:Journal of chemical theory and computation 2017-10, Vol.13 (10), p.5039-5053
Main Authors: Schmalhorst, Philipp S, Deluweit, Felix, Scherrers, Roger, Heisenberg, Carl-Philipp, Sikora, Mateusz
Format: Article
Language:English
Subjects:
Agglomeration
Biological activity
Carbohydrates
Dynamic structural analysis
Macromolecules
Molecular chains
Molecular dynamics
Molecular structure
Oligosaccharides
Osmosis
Polysaccharides
Regulators
Simulation
Virial coefficients
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Summary:Polysaccharides (carbohydrates) are key regulators of a large number of cell biological processes. However, precise biochemical or genetic manipulation of these often complex structures is laborious and hampers experimental structure–function studies. Molecular Dynamics (MD) simulations provide a valuable alternative tool to generate and test hypotheses on saccharide function. Yet, currently used MD force fields often overestimate the aggregation propensity of polysaccharides, affecting the usability of those simulations. Here we tested MARTINI, a popular coarse-grained (CG) force field for biological macromolecules, for its ability to accurately represent molecular forces between saccharides. To this end, we calculated a thermodynamic solution property, the second virial coefficient of the osmotic pressure (B 22). Comparison with light scattering experiments revealed a nonphysical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the nonbonded solute–solute, solute–water, and water–water interactions. This finding also applies to smaller oligosaccharides which were all found to aggregate in simulations even at moderate concentrations, well below their solubility limit. Finally, we explored the influence of the Lennard-Jones (LJ) interaction between saccharide molecules and propose a simple scaling of the LJ interaction strength that makes MARTINI more reliable for the simulation of saccharides.
ISSN:1549-9618
1549-9626
DOI:10.1021/acs.jctc.7b00374