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, most currently used MD force fields overstate non-bonded interactions between polysaccharide molecules, strongly limiting 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 that MARTINI strongly overestimates non-bonded interactions for a prototypic polysaccharide , leading to unrealistic aggregation . 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.
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 non-physical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the non-bonded 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.
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most
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overstate non-bonded interactions between polysaccharide molecules, strongly limiting
often overestimate the aggregation propensity of polysaccharides, affecting
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that MARTINI strongly overestimates
a non-physical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the
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interactions for a prototypic polysaccharide
solute-solute
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leading to unrealistic aggregation
solute-water, and water-water interactions