MAOB is an enzyme located on the outer mitochondria that is responsible for degrading penylethylamine, benzylamine, and dopamine. MAOB inhibitors are generally used as a treatment for Parkinson’s disease because they stop the breakdown of dopamine. By selectively designing an inhibitor for the MAOB enzyme, the breakdown of dopamine can be reduced leading to an increase of the neurotransmitter. A suite of dopaminergic derivatives have been developed as potential inhibitors of the MAOB enzyme. The inhibitory effectiveness of these dopaminergic derivatives has been measured via in silico models in which the strength of interaction between each substrate and the enzymatic active site was analyzed. A crystal-structure of the MAOB active site, docked with the widely employed diabetes drug pioglitazone, was isolated from the Protein Data Bank (PDB ID: 4A79). The positions of novel dopaminergic derivatives were optimized in the active site using M062X/6-31G with implicit solvation and with relaxed amino acid side-chains. Interaction energies between the ligands and the protein were calculated using M062X and MP2 with the 6- 311+G* basis set. At present, we have seen a strong correlation between positively charged inhibitors and attractive negative interaction energies.<br/>

DFT study of the selectivity of monoamine oxidase B

255th National Meeting (2018)

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