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

Area of Science:

• Biophysics
• Computational Chemistry
• Materials Science

Background:

• Hyaluronan (HA) is a vital glycosaminoglycan involved in tissue structure, hydration, and cellular functions.
• Accurate molecular models are needed to study HA's complex roles in biological systems.

Purpose of the Study:

• To develop and validate a coarse-grained (CG) model for hyaluronic acid (HA) and its constituent residues.
• To ensure compatibility with the Martini 3 force field for large-scale simulations.

Main Methods:

• Developed a CG model for HA, N-acetyl-d-glucosamine (GlcNAc), and glucuronic acid (GlcA).
• Validated the model against atomistic simulations, including free energy calculations.
• Simulated HA self-assembly, persistence length, and interactions with lipid bilayers and proteins.

Main Results:

• The CG model accurately reproduces bonded interactions and transfer free energies.
• Simulations showed correct HA self-assembly behavior and persistence length.
• The model effectively captures HA interactions with lipid bilayers and HA-binding proteins.

Conclusions:

• The new CG Martini 3 model enables large-scale simulations of HA-containing systems.
• This model enhances understanding of hyaluronan's functions in biological contexts.
• The model is a valuable tool for studying hyaluronan's role in biomolecular systems.