Docking studies on monoamine oxidase-B inhibitors:: Estimation of inhibition constants (Ki) of a series of experimentally tested compounds

Monoamine oxidase (EC1.4.3.4; MAO) is a mitochondrial outer membrane flavoenzyme that catalyzes the oxidation of biogenic amines. It has two distinct isozymic forms designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant and neuroprotective drugs. Elucidation of the X-ray crystallographic structure of MAO-B has opened the way for molecular modeling studies. A series of experimentally tested (1-10) model compounds has been docked computationally to the active site of the MAO-B enzyme. The AutoDock 3.0.5 program was employed to perform automated molecular docking. The free energies of binding (Delta G) and inhibition constants (K-i) of the docked compounds were calculated by the Lamarckian Genetic Algorithm (LGA) of AutoDock 3.0.5. Excellent to good correlations between the calculated and experimental K-i values were obtained. (c) 2005 Elsevier Ltd. All rights reserved.