Phylogenetics and Molecular Docking Studies on Glycogen Phosphorylase Inhibitors as Anti-Diabetic Agents
Main Article Content
Abstract
Glycogen phosphorylase (GP) is a key enzyme involved in glycogen breakdown, making it a critical target for regulating blood glucose levels, particularly in the context of diabetes mellitus. This study combines phylogenetic analysis and molecular docking techniques to identify potential inhibitors of GP as anti-diabetic agents. Phylogenetic analysis was conducted to explore the evolutionary relationships of liver GP from Homo sapiens, highlighting conserved regions that may be crucial for inhibitor binding. The 3D structure of the GP enzyme (1FA9) was retrieved from the Protein Data Bank and used for molecular docking studies with a range of plant-derived compounds. Seventeen ligands were evaluated, and docking results revealed that several compounds displayed strong binding affinities at the active site with its native ligands Pyridoxal Phosphate and Adenosine monophosphate; with the average binding energy reaching around -8 kcal/mol. Kaempferol, Momordenol, and Loganic Acid may have stronger interactions due to the higher number of residues they interact with. Lys574, Thr676, and Gly677 appear to be critical residues in the protein's active or binding site, as they interact with multiple compounds. These findings suggest that the selected plant-based compounds may serve as effective GP inhibitors and offer potential as lead compounds for the development of anti-diabetic drugs. This study underscores the value of integrating phylogenetics and molecular docking in the discovery of novel therapeutic agents for diabetes.