Journal of Chemical Theory and Computation
Journal of Chemical Theory and Computation
5 years ago

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

Overcoming the Limitations of the MARTINI Force Field in Simulations of Polysaccharides
Carl-Philipp Heisenberg, Felix Deluweit, Philipp S. Schmalhorst, Mateusz Sikora, Roger Scherrers
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 (B22). 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.

Publisher URL: http://dx.doi.org/10.1021/acs.jctc.7b00374

DOI: 10.1021/acs.jctc.7b00374

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