Journal of Advanced Bioinformatics Applications and Research ISSN 0976-2604 Vol 2, Issue 1, 2011, pp 108-120 http://www.bipublication.com HOMOLOGY MODELING OF CATECHOL-O- METHYLTRANSFERASE (COMT) BY USING INSILICO APPROACH Vaibhav B. Sabale 1* , Sonali B. Meshram 2 . 1,2 International Institute of Information Technology (I2IT), Hinjawadi, Pune 1 Research Officer, Bioinput Department, Nirmal Seeds India Pvt. Ltd. Pachora, Dist- Jalgaon, MH, India. 2 Scientist, Bhat Biotech India Pvt. Ltd., Bangalore, Karnataka, India ABSTRACT: COMT is main enzyme responsible for metabolism of Levodopa. Levodopa is a drug treatment for the Parkinson’s disease. This disease cause due to loss of Dopamine in brain. Dopamine is chemical messenger or cell signaling which transfer the signal, brain to all over body parts for the movement. It is neurotransmitter which present in substanic nigra. Damage in area of brain that control muscle movement cause a decrease in dopamine production also the less synthesis of dopamine. The catechol O- methyltransferase COMT gene contains a functional polymorphism Val158Met wise has been related to common disease like cancer, psychiatric illness ,etc Val158Met has been found to influence human pain perception. The COMT susceptible to schizophrenia. COMT is main enzyme responsible for metabolism of Levodopa, Dopmine other catecholamines and their metabolism. COMT catlyzes the transfer of methyl group from S-adenosy L-methionine (SAM) to hydroxyl group of cathecolamine. Catechol-O-methyltransferase (COMT) inactivates catecholamines and catechol drugs such as L-DOPA. A common genetic polymorphism in humans is associated with a three-to-four-fold variation in COMT enzyme activity and is also associated with individual variation in COMT thermal instability. We now show that this is due to G-->A transition at codon 158 of the COMT gene that results in a valine to methionine substitution. Keywords: COMT, Homology modeling, Dopamine, Model building [I] Introduction Parkinson's disease (PD) is a gradual progressive central neurodegenerative disorder that affects body movement and is characterized by symptoms such as muscle rigidity, resting tremors, loss of facial expression, hypophonia, diminished blinking, and akinesia. Parkinsonian like central nervous system (CNS) disorders usually involve the pigmented neuronal systems of the brainstem, particularly the zona compacta of the substantia nigra which gives rise to the dopaminergic nigrostriatal pathway and the locus ceruleus giving rise to a noradrenergic pathway.[1] The motor disabilities characterizing PD are primarily due to the loss of dopaminergic neurons in the substantia nigra resulting in a dramatic decrease in the dopamine levels in the brain. Once the DA neuronal cell death reaches the critical level of 85-90%, the neurological symptoms of PD appear. The current treatment for PD is the systematic administration of levodopa (L- DOPA), a precursor to DA which enters the brain via a carrier - mediated transport system where it is converted to DA by the enzyme L-aromatic amino acid decarboxylase (L-AAAD). Since the discovery in the 1960s that striatal dopamine is deficient in PD and it's replacement with high dosages of L-DOPA could ameliorate the symptoms of parkinsonism, research on PD has increased dramatically. Since its discovery in 1958 (Axelrod and Tomchick 1958), catechol-O- methyltransferase (COMT) has been an important enzyme in catecholamine biochemistry and pharmacology and, more recently, in genetic mechanisms of variation in catechol metabolism and its clinical implications. [2] COMT catalyzes the transfer of a methyl group from S-adenosyl- methionine (SAM) to a hydroxyl group on a catechol nucleus (e.g., dopamine, norepinephrine, or catechol estrogen). Genetic variation in COMT has been associated with diverse clinical