  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.
