Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

Frontiers in Chemistry
Aman Chandra KaushikShakti Sahi

Abstract

GPR142 (G protein receptor 142) is a novel orphan GPCR (G protein coupled receptor) belonging to "Class A" of GPCR family and expressed in β cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling, and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading andab initiomethods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

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Citations

May 11, 2021·3 Biotech·Muthu Kumar ThirunavukkarasuRamanathan Karuppasamy

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Datasets Mentioned

BETA
NP-861455.1

Methods Mentioned

BETA
X-Ray

Software Mentioned

LigPrep
OPLS2005
Sitemap
HTVS
Modeler
TMbase
Glide Schrodinger suite
Desmond package
Schrodinger suite
Schrödinger

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