Abstract / Summary
Abstract This study investigates the potential binding of fluoxetine to the enzyme dipeptidyl peptidase-4 (DPP-4) using computational approaches. Molecular docking and structural analysis were performed using PyMOL, AutoDock Vina, RDKit, and Avogadro 2. The docking protocol was first validated by removing the native ligand from the DPP-4 crystal structure and subsequently redocking it into the binding site using an exhaustiveness value of 64. Nine docking poses were generated, with the highest predicted binding affinity being −8.4 kcal/mol. Among these poses, pose 4 showed particularly strong agreement with the crystallographic binding mode, producing an RMSD of 0.546 Å and a docking score of −8.2 kcal/mol. This result indicates that the docking protocol was capable of reproducing the experimentally observed ligand-binding pose with a high degree of accuracy.The docking results for fluoxetine, discussed later in this paper, predicted a best binding affinity of −7.7 kcal/mol.Consistent results were obtained using exhaustiveness values of both 64 and 32, supporting the reproducibility of the predicted docking outcome. These findings suggest that fluoxetine may be capable of binding within the DPP-4 binding site.This observation may provide a potential molecular mechanism worthy of further investigation in relation to reports ofaltered blood glucose levels in some patients with type 2 diabetes receiving fluoxetine. However, molecular docking alone cannot establish DPP-4 inhibition or a therapeutic effect, and experimental validation would be required. Additionally fluoxetine was redocked again with the help of Autodock4 to independently verify the docking.AI tools were used intermittently during this study for coding assistance, literature exploration, language refinement, and methodological guidance. Information obtained through AI assistance was independently reviewed and verified where possible, and the author assumes full responsibility for the accuracy and interpretation of the final work.Multiple papers are cited many times in this paper so it may appear as though the citations are not sequential but they are and repeating numbers are just the same paper being cited again.