Molecular docking approach of monoamine oxidase B inhibitors for identifying new potential drugs: Insights into drug-protein interaction discovery

Monoamine oxidase (EC, 1.4.3.4) or amine oxidoreductase catalyzes the oxidative deamination of biogenic amines. Abnormal action of the monoamine oxidase B has been associated with neurological dysfunctions including parkinson´s disorder. Monoamine oxidase B inhibitors divulged that these agents were effective in the therapeutic management of Parkinson's disease. Understanding the interaction of monoamine oxidase binding site with inhibitors is crucial for the development of pharmaceutical agents. At the molecular docking, the exact prediction of the binding modes between the inhibitors and protein is of central importance in structure-based drug design. In the current study, we examined two classes of monoamine oxidase B inhibitors. We applied Autodock tools 4.2, in order to set up the docking runs and predict the inhibitors binding free energy. The final product of molecular docking was clustered to specify the binding free energy and optimal docking energy conformation that is investigated as the best docked structure. Docking results indicate that the contribution of van der Waals interactions is greater than electrostatic interactions so that, it can be concluded that all of the inhibitors attached to a hydrophobic binding site in monoamine oxidase B. Among the total of molecules tested, it was proved that 2-(2-cycloheptylidenehydrazinyl)-4-(2,4-dichlorophenyl)-1,3-thiazole has the lowest binding free energy and the lowest Van der Waals energy and also the lowest inhibition constant and subsequently the most experimental affinity. As well as, we find out a possible relationship between the estimated results and experimental data. The selective information from this work is crucial for the rational drug design of more potent and selective monoamine oxidase B inhibitors based on the 8-benzyloxycaffeine scaffold

کلیدواژه ها:

monoamine oxidase B inhibitor ، Parkinson´s disorder ، molecular docking ، binding free energy