Extending the Martini 3 Coarse-Grained Force Field to Carbohydrates

Abstract

Carbohydrates play an essential role in a large number of chemical and biochemical processes. High structural diversity and conformational heterogeneity make it problematic to link their measurable properties to molecular features. Molecular dynamics simulations carried out at the level of classical force fields are routinely applied to study the complex processes occurring in carbohydrate-containing systems, while the usefulness of such simulations relies on the accuracy of the underlying theoretical model. In this article, we present the coarse-grained force field dedicated to glucopyranose-based carbohydrates and compatible with the recent version of the Martini force field (v. 3.0). The parameterization was based on optimizing bonded and nonbonded parameters with a reference to the all-atom simulation results and the experimental data. Application of the newly developed coarse-grained carbohydrate model to oligosaccharides curdlan and cellulose displays spontaneous formation of aggregates of experimentally identified features. In contact with other biomolecules, the model is capable of recovering the protective effect of glucose monosaccharides on a lipid bilayer and correctly identifying the binding pockets in carbohydrate-binding proteins. The features of the newly proposed model make it an excellent candidate for further extensions, aimed at modeling more complex, functionalized, and biologically relevant carbohydrates.