Extending the Martini 3 Coarse-Grained Force Field to Hyaluronic Acid

Hyaluronan, also known as hyaluronic acid, is a large
glycosaminoglycan
composed of repeating disaccharide units. It plays a crucial role
in providing structural support, hydration, and facilitating cellular
processes in connective tissue, skin, and the extracellular matrix
in biological systems. We present a coarse-grained (CG) model of hyaluronic
acid (HA) and its constituent residues, N-acetyl-d-glucosamine (GlcNAc) and glucuronic acid (GlcA), designed
to be compatible with the Martini 3 force field. The model was validated
against atomistic molecular dynamics simulations following standard
procedures to ensure the accuracy of bonded interactions and, in the
case of GlcNAc, the free energies of transfer between octanol and
water. For the final HA model, we investigated its properties by simulating
the self-assembly of HA chains at varying ion concentrations in solution
and comparing the persistence length of single-chain HA with experimental
data. We also studied the interactions of HA with lipid bilayers and
various HA-binding proteins, demonstrating the ability of the model
to accurately reproduce interactions with other biomolecules characteristic
of natural biological systems. This extension of the carbohydrate-dedicated
branch of the CG Martini 3 force field enables large-scale molecular
dynamics simulations of HA-containing systems and contributes to a
better understanding of the roles and functions of hyaluronan in natural
biomolecular systems.