Computational identification of novel natural inhibitors of glucagon receptor for checking type II diabetes mellitus — ASN Events
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Computational identification of novel natural inhibitors of glucagon receptor for checking type II diabetes mellitus (#16)

Sonam Grover 1 , Jaspreet Kaur Dhanjal 1 , Sukriti Goyal 2 , Abhinav Grover 3 , Durai Sundar 1
  1. Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi, India
  2. Apaji Institute of Mathematics & Applied Computer Technology, Banasthali University, Tonk, Rajasthan, India
  3. School of Biotechnology, Jawaharlal Nehru University, Delhi, India

Background

Interaction of the small peptide hormone glucagon with glucagon receptor (GCGR) stimulates the release of glucose from the hepatic cells during fasting; hence GCGR performs a significant function in glucose homeostasis. Inhibiting the interaction between glucagon and its receptor has been reported to control hepatic glucose overproduction and thus GCGR has evolved as an attractive therapeutic target for the treatment of type II diabetes mellitus.

Results

In the present study, a large library of natural compounds was screened against 7 transmembrane domain of GCGR to identify novel therapeutic molecules that can inhibit the binding of glucagon with GCGR. Molecular dynamics simulations were performed to study the dynamic behaviour of the docked complexes and the molecular interactions between the screened compounds and the ligand binding residues of GCGR was analysed in detail. We report two natural drug like compounds PIB and CAA which showed good binding affinity for GCGR and are potent inhibitor of its functional activity.

Conclusion

This study contributes evidence for application of these compounds as prospective small ligand molecules against type II diabetes. Novel natural drug like inhibitors against the 7 transmembrane domain of GCGR have been identified which showed high binding affinity and potent inhibition of GCGR.