AlphaFold 3.0 Prediction Reveals Stronger Interaction between Oleic Acid and Colipase than Palmitic Acid

Abstract

The interaction between colipase and lipase is known to be crucial for lipid digestion, but the roles of other factors remain unclear. This study explores the dynamics of pancreatic lipase hydrolysis facilitated by colipase, with a focus on the regulatory roles of fatty acids and calcium ions. Using computational modeling, including insights from AlphaFold 3.0, we elucidate the structural interactions essential for hydrolysis activity. The prediction highlights the significant role of calcium ions in altering the interaction between fatty acids and the lipase–colipase complex, thereby changing catalytic efficiency. We further demonstrate that slower hydrolysis rates are associated with a stronger binding affinity between colipase and oleic acid, as well as the occupation of the lipase catalytic pocket by oleic acid in the presence of calcium ions. The AlphaFold predictions provide a robust framework for experimental validation and potential applications. These findings offer deeper insights into dietary lipid digestion and highlight potential avenues for interventions addressing lipid digestion in malnutrition.