Molecular simulation for food protein–ligand interactions: A comprehensive review on principles, current applications, and emerging trends

Abstract In recent years, investigations on molecular interaction mechanisms between food proteins and ligands have attracted much interest. The interaction mechanisms can supply much useful information for many fields in the food industry, including nutrient delivery, food processing, auxiliary detection, and others. Molecular simulation has offered extraordinary insights into the interaction mechanisms. It can reflect binding conformation, interaction forces, binding affinity, key residues, and other information that physicochemical experiments cannot reveal in a fast and detailed manner. The simulation results have proven to be consistent with the results of physicochemical experiments. Molecular simulation holds great potential for future applications in the field of food protein–ligand interactions. This review elaborates on the principles of molecular docking and molecular dynamics simulation. Besides, their applications in food protein–ligand interactions are summarized. Furthermore, challenges, perspectives, and trends in molecular simulation of food protein–ligand interactions are proposed. Based on the results of molecular simulation, the mechanisms of interfacial behavior, enzyme‐substrate binding, and structural changes during food processing can be reflected, and strategies for hazardous substance detection and food flavor adjustment can be generated. Moreover, molecular simulation can accelerate food development and reduce animal experiments. However, there are still several challenges to applying molecular simulation to food protein–ligand interaction research. The future trends will be a combination of international cooperation and data sharing, quantum mechanics/molecular mechanics, advanced computational techniques, and machine learning, which contribute to promoting food protein–ligand interaction simulation. Overall, the use of molecular simulation to study food protein–ligand interactions has a promising prospect.