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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Event Hall |
| Time |
4월 19일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-648 |
| Subject |
Molecular Dynamics Simulation Study of SHIP2 |
| Authors |
Changdev G Gadhe, Ae Nim Pae1,*, Ashwini Londhe2
Convergence Research Center for Dementia DTC, Korea Institute of Science and Technology, Korea
1Korea Institute of Science and Technology, Korea
2University of Science & Technology, Korea
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| Abstract |
SH2-containing-inositol-5-phosphatases (SHIPs) dephosphorylate the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) and play an important role in regulating the PI3K/Akt pathway in physiology and diseases such as type 2 diabetes and obesity. Targeting SHIP2 also presents a helpful therapeutic approach in treating neurodegenerative disease and atherosclerosis. The SHIP Ptase domain belongs to a family of Mg2+-dependent inositol phosphatases with specificity for 5 P dephosphorylation of inositol rings. Recently, few X-ray structures reported with the small molecule allosteric inhibitors. However, information about catalytic binding site residues remains elusive. With the aim to unravel the molecular mechanism and crucial interaction between SHIP2 catalytic binding site and synthetic ligands, we performed docking and molecular dynamics (MD) simulation study. Known ligands selected for the experiment, Discovery Studio program used to dock the known ligands and Gromacs-5.0.6 package installed at KISTI supercomputer was used to perform MD simulation study. Docking guided MD simulation results revealed that during MD simulation new residues were incorporated surrounding ligands and stabilized through an extensive network of interactions. Crucial residues identified in the catalytic domain, and this information could be exploited in future to design novel and potent SHIP2 inhibitors which might help therapeutic benefits in neurodegenerative diseases. |
| E-mail |
F07338@kist.re.kr |
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121st General Meeting of the KCS