Investigating Eugenol-Lysozyme complex using docking and molecular dynamic simulation methods

Amyloid fibrils are -sheet rich protein aggregates with fibrillar morphology which are a challenge in amyloidosis and recombinant protein technology. Various small molecules inhibit fibrillation process of different proteins. In this study, the effect of eugenol, a natural ingredient of cloves, on hen egg-white lysozyme (HEWL), a model system for amyloid fibrillation, was assessed using molecular docking and molecular dynamic (MD) simulations. Blind docking, using AutoDock۴, showed a binding energy of -۴.۹۹ kcal/mol. The critical amino acid residues for forming Eugenol-lysozyme complex by hydrogen bonding (Asp۵۲ and Val۱۰۹) and hydrophobic interactions (Gln۵۷, Ile۵۸, Asn۵۹, Trp۶۳, Ala۱۰۷ and Trp۱۰۸) were revealed. These residues constitute the aggregation prone region (APR) of the protein. Afterwards, the lowest docking energy structure was selected for more investigation using MD simulations lasting ۲۰۰ ns using GROMACS۲۰۱۹.۶ software and Amber۹۹SB force field. Parameters such as root-mean square-deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg) and solvent accessible surface area (SASA) were evaluated. RMSD and RMSF of the enzyme in the presence of eugenol decreased in comparison to the enzyme alone. Moreover, the presence of eugenol increases the number of intramolecular hydrogen bonding of lysozyme. On the other hand, eugenol effect on SASA and Rg of the enzyme were insignificant. Thus, it seems that eugenol does not drastically alter the structure of the protein. In conclusion, eugenol showed a potential to interfere with the fibrillation process of lysozyme.

کلیدواژه ها:

Amyloid fibrillation ، Eugenol ، Lysozyme ، Molecular dynamic ، Small molecule inhibitors ، Simulation