Charge distribution defines the mechanism of fish gelatin-polysaccharide interactions

The molecular mechanisms of fish gelatin (FG)-polysaccharide interactions are crucial for designing of advanced biomaterials. While experimental studies have demonstrated that polysaccharides can enhance the FG's functional properties, the atomic-level details of these interactions remain poorly characterized. In this study, we employ molecular docking to identify preferential binding sites of gelatin and the all-atom molecular dynamics (MD) simulations to quantify the interaction energetics and complex stability, with particular focus on the role of local charge distribution along gelatin molecule. We modeled four FG fragments with varying charge distribution and analyzed their interactions with anionic and cationic polysaccharides ι-carrageenan, alginate and chitosan. The MD simulations revealed that the charge density patterns of both interacting molecules critically determine gelatin-polysaccharide binding affinity and complex stability. This work provides first 3D-structural models of FG-polysaccharide complexes, offering fundamental insight for biomaterial design.