Investigation on Binding Interactions Between Extracellular Amino-terminal Domain of GLP-1 Receptor Mutations and GLP-1 by Molecular Dynamics Simulations

Binding interactions between the extracellular amino-terminal domain (ECD) of glucagon-like pep-tide-1(GLP-1) receptor and GLP-1 were studied by molecular dynamics simulations. As shown in calculation results, the binding ligand led to conformational changes of the receptor. Pro90 and Trp91 in Loop2 and G1u128 in the C-terminus moved towards the ligand upon ligand binding. The receptor ECD was mutated in some conserved residues(P73A, V81L, Y88A, P90A and W91A), whose structures and flexibilities have changed violently. Mutations of Trp91 and Tyr88 led to complete loss of binding affinity of the ligand and the effects of those mutations were discussed elaborately. Given all the results, there was no big difference between the interactions related to the receptor ECDP73A and the wild type, which suggested that Pro73 was not vital for ligand binding, while mutation of V88L might make a complete affinity loss of GLP-1.