In-Silico Design of Novel Glucagon-Like Peptide 1 Mutants as Candidate for New Peptide Agonist Drugs
The binding of glucagon-like peptide 1 (GLP-1) incretin hormone and its receptor GLP-1R plays an important role in the human body. The GLP-1 acts as the insulin secretion stimulator through a GLP-1R agonist activation to avoid the type 2 diabetes mellitus problem. A recent development in computational sciences has enabled us to design a new GLP-1 mutant which has a better binding stability to GLP-1R. In this paper, we have conducted an in-depth analysis of protein-protein docking of GLP-1 and GLP-1R receptor to determine the responsible factors affecting the binding stability. The protein-protein binding stability was analyzed by performing the point mutations on the GLP-1 structure and running the molecular dynamics simulation of the docked structures. Five mutants, Lys20Arg, Lys20His, Lys20Ser, Lys20Gly, and Lys20Ala, has been created computationally and docked with GLP-1R and tested via a molecular dynamics simulation and the free energy perturbation calculation to search for the best-binding mutant. Our results have shown that the Lys20His mutant design has the best potential to be developed as a new peptide agonist drug based on its binding affinity and structural integrity as compared to other mutants and the peptide agonist drugs available in the market exenatide, and liraglutide.
Copyright (c) 2021 Tony Sumaryada, Ajeng Widya Roslia, Alfi Afifah, Setyanto Tri Wahyudi, Agus Kartono
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