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| Type |
Poster Presentation |
| Area |
의약화학 |
| Room No. |
포스터발표장 |
| Time |
4월 20일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-464 |
| Subject |
Insights into the Interaction Mechanism of NAM and mGluR2: A Computational Modeling Approach |
| Authors |
Gadhe Changdev Gorakshnath, 배애님1,*
한국과학기술연구원(KIST) 치매DTC융합연구단, Korea
1한국과학기술연구원(KIST) 생체과학연구본부, Korea
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| Abstract |
Allosteric modulation of G protein-coupled receptors (GPCRs) represents a novel strategy for the development of subtype-specific therapeutics for the central nervous system target receptors. The metabotropic glutamate receptor 2 (mGluR2) is a class C GPCRs that plays an important role in neuro-modulatory brain functions. mGluR2 is an attractive drug target for the therapeutic intervention of neurodegenerative disorders including anxiety, depression, Fragile X Syndrome, Parkinson’s disease and schizophrenia. Unavailability of mGluR2 X-ray structure and implications in various neurodegenerative disease prompted us to initiate the computational modeling study. Therefore, we perform homology modeling to develop 3D-model of mGluR2. Computational docking studies of negative allosteric modulators (NAM) was executed in the predefined binding site. Ligand-protein complexes were embedded in hydrated palmitoyloleoylphosphatidylcholine (POPC) lipid bilayers, and these systems were simulated via molecular dynamics (MD) simulations to get robust, relaxed and better binding modes. Analyses of binding modes were performed, and pharmacophore models were developed and validated. Pharmacophore models were served to screen chemical libraries to get novel hits. ADMET filters were used to reduce the data size and compounds were purchased for biological testing. In future, lead optimization to be performed to get novel mGluR2 allosteric modulators for its therapeutic benefits in neurodegenerative disorder. |
| E-mail |
F07338@kist.re.kr |
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119th General Meeting of the KCS