Molecular docking of inhibitors into monoamine oxidase B.
Monoamine oxidase B (MAO-B) functions in the deamination of monoamines, including dopamine and norepinephrine. The search for MAO-B inhibitors increased following the discovery that the enzyme may be responsible for generating neurotoxins from various endogenous or exogenous compounds. Computational screening methods aid in the search for new inhibitors, but validation studies for specific software packages and receptors are necessary for effective application of these methods. In this study, DOCK 6.0.0 was used to dock a series of inhibitors to MAO-B. Included were studies of re-docking ligands into MAO-B crystal structures, after which a set of 30 compounds with known inhibition constants for MAO-B were docked, including 15 strong inhibitors and 15 weak inhibitors. Good agreement was observed between the top experimental inhibitors and the top ranked docking results, and key interactions between the ligands and receptor were identified.
Harkcom
William T
WT
Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Bevan
David R
DR
D001665:Binding Sites; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000648:ultrastructure*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry*; D011485:Protein Binding; D020539:Sequence Analysis, Protein / Q000379:methods*; D013329:Structure-Activity Relationship
D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase