In silico identification of Aloe-derived anthraquinones as potential PTP1B inhibitors: Docking and structural dynamics insights

Abstract

Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling pathway and is widely recognized as a target for treatment in type 2 diabetes. Aloe-derived anthraquinones are known for several biological activities, however their ability to inhibit PTP1B has not yet been studied in facet through computational studies. In the present study, Lipinski’s Rule of Five was used to determine if aloe anthraquinones possess drug-like properties. The study utilized AutoDock 4 to carryout molecular docking, with PTP1B (PDB ID: 2QBP) as the protein target. The study also investigated the changes in conformation via procedures such as RMSD and RMSF. The study assessed the structural integrity and adaptability of the docked complex by analyzing its radius of gyration, the extent of solvent-accessible surface area, and by comparing secondary structure. Several aglycone derivatives met Lipinski’s standards, in contrast the glycosylated compounds did not comply. The docking results suggested that aloe-emodin O-acetyl posess the notable binding affinity and established stable interactions with key catalytic residues, including Cys215, Arg221, and Tyr46. Structural analyses demonstrated that the WPD loop imparts small change in shape, less adaptability, and robust global folding when a ligand bound to it. The results altogether demonstrate that aloe-emodin O-acetyl effectively stabilizes important catalytic domains of PTP1B without altering the general arrangement of the protein. This supports its potential as a lead PTP1B inhibitor. Anthraquinones from aloe are promising leads for the development of new antidiabetic drugs.