Deciphering the Interaction of 5,7‐Dihydroxyflavone with Hen‐Egg‐White Lysozyme through Multispectroscopic and Molecular Dynamics Simulation Approaches

• Published in: ChemistrySelect (Weinheim) Vol. 3; no. 17; pp. 4911 - 4922
• Main Authors: Das, Sourav, Khanikar, Portia, Hazarika, Zaved, Rohman, Mostofa Ataur, Uzir, Antara, Nath Jha, Anupam, Singha Roy, Atanu
• Format: Journal Article
• Language: English
• Published: 08-05-2018
• Subjects: Chrysin; Circular Dichroism; Fluorescence; HEWL; Molecular Dynamics (MD) Simulation
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201800280

In recent times, research based on the bio‐active flavonoid, chrysin has shown its potential therapeutic applications such as anti‐diabetic, neuroprotective, anti‐asthmatic, anti‐depressant, etc. In order to understand its molecular recognition process, we studied its interaction with hen egg white lysozyme (HEWL) at physiological conditions. Chrysin (5,7‐Dihydroxyflavone) was able to quench the intrinsic fluorescence of HEWL through static quenching mechanism and the binding constant (Kb) was found to be (4.390±0.088 ×104) M−1 at 298 K and it decreased with the increase in temperature. The value of thermodynamic parameters such as ΔH (‐17.154±0.872) kJ mol−1 and ΔS (+31.267±3.151) J K−1 mol−1 indicated that hydrogen bonding and hydrophobic forces played a central role in the complexation process. Alteration in the Trp micro‐environment was induced due to the incorporation of chrysin in the binding site as indicated by synchronous and three dimensional (3D) fluorescence studies. FT‐IR and CD studies revealed that the secondary structure of HEWL was altered on chrysin binding, which resulted in an increase in the α‐helical stability of the protein. Chrysin inhibited the enzymatic activity of HEWL against M. lytus. Molecular docking and molecular simulation studies revealed that hydrogen bonding and hydrophobic forces played a vital role in complexation process. This study provides substantial insight into the binding of a bio‐active flavonoid (chrysin) with a carrier protein (HEWL).
In the present study, we have demonstrated the interaction of a bioactive flavonoid, chrysin with HEWL. Chrysin interacted with HEWL through static quenching mechanism while hydrogen bonding and hydrophobic forces played a vital role in the complexation process. Chrysin was also found to cause slight conformational changes within the structure of protein during binding. Molecular docking and molecular dynamics simulation studies indicated that chrysin binds within the substrate binding site of HEWL.