University of Limerick
Shubham_Vishnoi_Poster.pdf (5.26 MB)

Rational design of therapeutic peptides using physics-based molecular dynamics simulations

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Abstract: Peptides are sustainable alternatives to conventional therapeutics for G protein-coupled receptor (GPCR) linked disorders, promising biocompatible and tailorable next-generation therapeutics for metabolic disorders including type-2 diabetes, as agonists of the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R). However, single agonist peptides activating GLP-1R to stimulate insulin secretion also suppress obesity-linked glucagon release. Hence, bioactive peptides co-targeting GCGR and GLP-1R may remediate the blood glucose and fatty acid metabolism imbalance, tackling both diabetes and obesity to supersede current mono-agonist therapy. Here we design and model optimised peptide sequences starting from peptide sequences derived from earlier phage-displayed library screening, identifying those with predicted molecular binding profiles for dual agonism of GCGR and GLP-1R. We derive design rules from extensive molecular dynamics simulations based on peptide–receptor binding. Our newly designed co-agonist peptide exhibits improved coupled binding affinity for GCGR and GLP-1R relative to endogenous ligands, which may provide superior glycaemic and weight loss control.

Event Details:


The event showcased the breadth of research conducted in the Department and was an excellent opportunity for networking and engaging with the Physics community at UL.


Also affiliated with

  • Synthesis and Solid State Pharmaceutical Centre