Binding characteristics and conformational changes in alpha-2-macroglobulin by the dietary flavanone naringenin:...

In the present study, we investigated the interaction of alpha-2-macroglobulin (α2M) with naringenin using multi-spectroscopic, molecular docking, and molecular simulation approaches to identify the functional changes and structural variations in the α2M structure. Our study suggests that naringenin compromised α2M anti-proteinase activity. The results of absorption spectroscopy and fluorescence measurement showed that naringenin-α2M formed a complex with a binding constant of (k_b)∼10⁴, indicative of moderate binding. The value of ΔG° in the binding indicates the process to be spontaneous and the major force responsible to be hydrophobic interaction. The findings of FRET reveal the binding distance between naringenin and the amino acids of α2M was 2.82 nm. The secondary structural analysis of α2M with naringenin using multi-spectroscopic methods like synchronous fluorescence, red-edge excitation shift (REES), FTIR, and CD spectra further confirmed the significant conformational alterations in the protein. Molecular docking approach reveals the interactions between naringenin and α2M to be hydrogen bonds, van der Waals forces, and pi interactions, which considerably favour and stabilise the binding. Molecular dynamics modelling simulations also supported the steady binding with the least RMSD deviations. Our study suggests that naringenin interacts with α2M to alter its confirmation and compromise its activity.Communicated by Ramaswamy H. Sarma.