Targeting MAO-B selectivity: computational screening, docking, and molecular dynamics insights.

Monoamine oxidase B (MAO-B) is a key target in Parkinson's disease treatment due to its role in dopamine metabolism. This study applied a multi-stage in silico workflow - combining 3D-pharmacophore modelling, 2D-QSAR, ADMET filtering, docking, molecular dynamics (MD), and MM/PBSA analysis - to identify selective MAO-B inhibitors. From four datasets including ZINC, DrugBank, TCM, and UNPD, 22 top candidates were selected based on docking scores and predicted selectivity over MAO-A. MD simulations (200 ns) and binding free energy calculations identified four promising compounds - ZINC21285023, ZINC79651118, ZINC58283019, and UNPD89644 (crotafuran E)- that exhibited stable binding and favourable interactions with key residues such as Cys172 and Tyr435. These compounds demonstrated performance comparable to or better than safinamide and are strong candidates for further experimental validation as selective MAO-B inhibitors.