Structure-guided identification of dipeptides modulating PPARα-associated lipid metabolism

The structural basis for dipeptides modulating PPARα remains unclear. AlphaFold2 identified Ile-His as a candidate predicted to interact with a novel alternative binding site. In HepG2 cells, Ile-His and Phe-Ala reduced cholesterol accumulation, whereas Ala-Pro had no effect. These findings support the utility of structure-based prediction as a hypothesis-generating approach for identifying dipeptides associated with PPARα-related modulation of lipid metabolism.