Molecular Dynamics Simulation of Structural Assembly and Hydration of Hyaluronic Acid in Salt Aqueous Buffer.

Hyaluronic acid (HA) is a nonsulfonated glycosaminoglycan critical in tissue development, physiology, and disease processes. To develop biomimetic in vitro models based on HA, it is important to understand the interaction of this polymer in its pristine form and with physiological solvents. However, atomistic simulations of HA chains are computationally challenging, especially when studying interactions with salts. To tackle this challenge, this study combined quantum mechanical (QM) calculations and molecular dynamics (MD) simulations to investigate HA's structure and behavior. This multiscale approach balances accuracy and computational efficiency. QM calculations emphasize the role of weak noncovalent hydrogen bonds in stabilizing d-glucuronic acid with N-acetyl-d-glucosamine. MD results show that more HA layers lead to a larger structure, higher water sensitivity, and increased dynamic and interlayer complexity. Our QM and MD simulations shed light on the structural dynamics and interactions of HA polymers and HA hydrogels, aiding in their design and optimization for biomedical applications and bridging computational and experimental approaches.