LOOP MODELING, SEQUENCE AND STRUCTURE BASED MUTATIONAL ANALYSIS AND MOLECULAR DOCKING OF CLASS C-GPCR PROTEIN (GRM 3)
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Date
2018-09
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OUAT
Abstract
Recent studies suggest that agonists of group II metabotropic glutamate (mGlu) receptors
(mGlu2/3) have potential utility as novel therapeutic agents for treatment of psychiatric
disorders such as anxiety, Bipolar disorder and schizophrenia. Agonists of mGlu2/3
receptors block amphetamine- and phencyclidine (PCP)-induced hyperlocomotor activity
in rodents, two actions that may predict potential antipsychotic activity of these
compounds. We focused on the metabotropic glutamate receptor type 3 gene (GRM3)
which is a candidate for schizophrenia and Bipolar disorder susceptibility. In this study the
normal and mutated protein structures are prepared through discovery studio. The
mutations were analysed using several computational tools out of which the most damaging
disease causing SNPs were considered to construct the mutant protein. We have used
Dcgiv (full Agonist), LY341495 (Antagonist), MGS0039 (Antagonist), NAAG (full
Agonist) etc. as the selective drugs found from Guide to Pharmacologyto study their
interaction pattern with wild and mutant protein GRM3.Asper our study, LY341495 acts as
a potent and selective orthosteric antagonist for the group II metabotropic glutamate
receptors (mGlu2/3).The finding could be utility as a novel approach for the treatment of
schizophrenia and Bipolar Disorder.
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