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Bulletin of the Korean Chemical Society (BKCS)

ISSN 0253-2964(Print)
ISSN 1229-5949(Online)
Volume 26, Number 11
BKCSDE 26(11)
November 20, 2005 

Comparative Homology Modeling and Ligand Docking Study of Human Catechol-O-Methyltransferase for Antiparkinson Drug Design
Jee-Young Lee, Yangmee Kim*
Methyltransferase, COMT, SAM, Parkinson’s disease, Homology modeling
Catechol-O-methyltransferase (COMT, EC is an S-adenosylmethionine (SAM, AdoMet) dependent methyltransferase, and is related to the functions of the neurotransmitters in various mental processes, such as Parkinson’s disease. COMT inhibitors represent a new class of antiparkinson drugs, when they are coadministered with levodopa. Based on x-ray structure of rat COMT (rCOMT), the three dimensional structure of human COMT (hCOMT) was constructed by comparative homology modeling using MODELLER. The catalytic site of these two proteins showed subtle differences, but these differences are important to determine the characterization of COMT inhibitor. Ligand docking study is carried out for complex of hCOMT and COMT inhibitors using AutoDock. Among fifteen inhibitors chosen from world patent, nine models were energetically favorable. The average value of heavy atomic RMSD was 1.5 A. Analysis of ligand-protein binding model implies that Arg201 on hCOMT plays important roles in the interactions with COMT inhibitors. This study may give insight to develop new ways of antiparkinson drug.
1695 - 1700
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