Molecular docking and dynamic simulation studies of isoflavones inhibiting Lox-2 activity for reducing beany flavor in soybean seeds

Low-lipoxygenase soybean cultivars are highly desirable because lower lipoxygenase content in soybean seeds leads to better quality soybean-based products and oils that are free from off-flavor or beany flavor. The expression of the Lox-2 gene is mainly responsible for this flavor. Over the years, natural antioxidants have been tested biochemically to inhibit Lox-2 activity, but in-silico studies are still lacking. To investigate the structural basis of inhibition, site-specific docking, as well as molecular dynamics (MD) simulations, were performed. Molecular docking analysis revealed that daidzein and genistein could be effective Lox2 receptor inhibitors. Furthermore, docked complexes were subjected to 100 ns MD simulation studies to analyze the structural conformations and stability of the complex. The analysis demonstrated that daidzein formed a more stable complex with the Lox-2 receptor and showed a higher H-bond propensity with the Asp775 residue. We discovered that the initial conformation of Lox2-daidzein complex changed to a more stable conformation at the beginning of the MD simulation and remained stable until the end with minor fluctuations. Furthermore, our analysis suggested that daidzein acts as a potential Lox-2 inhibitor and is a better candidate compared to genistein, which could be used to solve the beany flavor problem in soybean.Communicated by Ramaswamy H. Sarma.