Monoamine oxidase B template: useful for virtual screening

Monoamine oxidase B (MAO-B) is an outer mitochondrial membrane-bound enzyme that catalyses the oxidative deamination of arylalkylamine neurotransmitters. Activated MAO-B has a critical role in the pathogenesis of Alzheimer's disease (AD), including the accumulation of amyloid plaques, formation of neurofibrillary tangles, and cognitive impairment via the destruction of cholinergic neurons. As such, MAO-B has been proposed as a potential target for AD drug design. To accelerate the development of new MAO-B inhibitors, MAO-B template based on the protein target of MAO-B inhibitors was developed in the present study which can be used for structure-based drug design or for virtual screening studies. Six crystallographic structures of MAO-B bound with the selective MAO-B inhibitor were selected and downloaded from RCSB Protein Data Bank which include 1OJA, 2BK4, 2V5Z, 2V60, 2V61 and 3PO7. The six MAO-B templates were constructed by using AutoDockTools suite program. The developed templates of MAO-B were cross- validated by redocking with native ligand, and by docking the other five MAO-B inhibitors by utilising AutoDock 4. The results indicated that all ligands showed the best match of the docked and the crystallographic binding orientation in the MAO-B template developed from 1OJA. The results showed the same configuration of each ligand bound to 1OJA template with average RMSD values less than 1.95 Å. The new MAO-B template reported here should prove to be a useful tool for structure-based drug design and virtual screening in searching for new MAO-B inhibitors.

 

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Publication History

Article published online:
16 November 2023