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

Abstract

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).

Molecular Dynamics Simulation for Mechanism Elucidation of Food Processing and Safety: State of the Art

“…During the flavonol-human salivary protein interaction, binding of quercetin 3-O-glucoside to the IB937 model peptide caused the local structural rearrangement (Ferrer-Gallego et al, 2016). The above simulations show that hydrogen binding always play a vital role in the interactions between bioactive compounds and proteins/peptides (Cala et al, 2012;Canon et al, 2015;Das et al, 2018) Apart from hydrogen bonding interactions, hydrophobic interactions are also very important in the complexation of proteins with other molecules. For instance, the carboxylate group of lauric acid interacts with Lys60 and Lys69, but the interactions may undergo fluctuations that result in the replacement of Lys69 by Asn88.…”

“…During the flavonol–human salivary protein interaction, binding of quercetin 3‐ O ‐glucoside to the IB937 model peptide caused the local structural rearrangement (Ferrer‐Gallego et al., ). The above simulations show that hydrogen binding always play a vital role in the interactions between bioactive compounds and proteins/peptides (Cala et al., ; Canon et al., ; Das et al., )…”

“…One of the recent achievements of MD simulations is that they revealed the interactions between food protein and other molecules (Edelman, Kusner, Kisiliak, Srebnik, & Livney, 2015;Liu et al, 2017;Miao et al, 2013;Miao, Jiang, Jiang, Zhang, & Li, 2015). Apart from the previously mentioned interactions between proteins and carbohydrates, MD simulations including interactions of proteins with other compounds like flavonoids have also been documented (Das et al, 2018;Sahihi, HeidariKoholi, & Bordbar, 2012). MD simulations describing interactions of proteins with flavonoids have helped to probe mechanisms of food proteinbased delivery systems under various food processing conditions.…”

An integrative approach using systems biology, mutational analysis with molecular dynamics simulation to challenge the functionality of a target protein

“…Molecular dynamics (MD) study allows us to understand the behavior of the protein with respect to time mimicking its behavior inside a cell (Das, Khanikar, et al, 2018;Karplus & McCammon, 2002;Nayak et al, 2019). An all-atom molecular dynamics simulations for the constructed ADSL tetramer and the tetramer complex with the AMP have been carried out for 100ns using the gromos54a7 force field in gromacs-2016.4 package (Van Der Spoel et al, 2005).…”

Identification and analysis of structurally critical fragments in HopS2

“…Such aspects are a subject of significant assessment. Molecular dynamics approach is one such technique which in blend with modelling techniques helps to understand the time based functioning of proteins as well as protein-ligand complexes [28][29][30][31]. The technique also finds use in evaluating stability of modelled structures in a way to reveal the dynamics and functional attributes [32][33][34].…”