Comparison of protein-glycosaminoglycan interactions in ff14sb/GLYCAM06j and CHARMM36m force fields

Glycosaminoglycans (GAGs) are long, anionic polysaccharides abundant in the extracellular matrix and lysosomes, where their electrostatic interactions with proteins are essential for biological function. Computational studies of GAG-containing systems remain challenging due to their significant charge density and conformational flexibility. Here we benchmark two widely used force fields, ff14SB/GLYCAM06 and CHARMM36m, for three experimentally characterized protein–GAG complexes. Both approaches reproduce the general structural and energetic features of GAG–protein interactions. ff14SB/GLYCAM06 yields highly stable trajectories and consistent energetic profiles, whereas CHARMM36m more accurately captures GAG-induced conformational dynamics. These results establish practical benchmarks for accurate atomistic simulations of GAG–protein assemblies and inform future developments in biomolecular force fields.