Binding mechanism of naringenin with monoamine oxidase - B enzyme: QM/MM and molecular dynamics perspective

Hunday Govindasamy; Sivanandam Magudeeswaran; Saravanan Kandasamy; Kumaradhas Poomani

doi:10.1016/j.heliyon.2021.e06684

Binding mechanism of naringenin with monoamine oxidase - B enzyme: QM/MM and molecular dynamics perspective

Heliyon. 2021 Apr 8;7(4):e06684. doi: 10.1016/j.heliyon.2021.e06684. eCollection 2021 Apr.

Authors

Hunday Govindasamy¹, Sivanandam Magudeeswaran¹, Saravanan Kandasamy¹, Kumaradhas Poomani¹

Affiliation

¹ Laboratory of Biocrystallography and Computational Molecular Biology, Department of Physics, Periyar University, Salem, 636 011, India.

Abstract

The reduced level of dopamine at midbrain (substantia nigra) leads to Parkinson disease by the influence of monoamine oxidation process of monoamine oxidase B (MAO-B) enzyme. This disease mostly affects the aged people. Reports outline that the naringenin molecule acts as an inhibitor of MAO-B enzyme and it potentially prevents the development of PD. To elucidate the binding mechanism of naringenin with MAO-B, we performed the molecular docking, QM/MM and molecular dynamics (MD) simulations. The molecular docking results confirm that the naringenin strongly binds with the substrate binding site of MAO-B enzyme (-12.0 kcal/mol). The low values of RMSD, RMSF and Rg indicate that the naringenin - MAO-B complex is stable over the entire period of MD simulation. Naringenin forms strong interaction with the orient keeper residue Tyr326 and other binding site residues Leu171, Glu206 and these interactions were maintained throughout the MD simulation. It is also important to block the function of MAO-B enzyme. The QM/MM study coupled with the charge density analysis reveals the charge density distribution and the strength of intermolecular interactions of naringenin-MAO-B complex. The above results suggest that this molecule is a potential inhibitor of MAO-B enzyme.

Keywords: Binding free energy; Molecular docking; Molecular dynamics; Monoamine oxidase; Naringenin; Parkinson's disease; QM/MM.