Exploring marine natural compounds: <i>In silico</i> investigation of <i>Halimeda tuna</i> natural compounds for PPAR-γ targeting in type 2 diabetes

Introduction: The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a crucial regulator of glucose metabolism and insulin sensitivity, making it a primary target for diabetes therapy. Halimeda tuna, a marine alga, has shown potential as a source of bioactive chemicals with possible anti-diabetic effects. However, there is little information on the particular interactions of H. tuna-derived natural compounds with PPAR-γ. This research aimed to find prospective lead compounds by molecular docking and to evaluate their stability and interaction dynamics with the PPAR-γ using molecular dynamics simulations. Methods: The natural compounds were downloaded from http://knapsack3d.sakura.ne.jp/, then refined based on Lipinski’s criteria, and optimized for molecular docking. The PPAR-γ macromolecule (PDB ID 1I7I) was also refined to retain only the receptor and its native natural compound (AZ2). Molecular docking was carried out using AutoDock 4.2 to analyze the binding energy and binding mode. To evaluate the stability of the natural compound-receptor complexes, molecular dynamics simulations were conducted for 100 ns using Gromacs 2023. Results: The molecular docking studies showed that the binding energies for M12 and M7 were -10.77 kcal/mol and -9.91 kcal/mol, respectively. However, when molecular dynamics (MD) simulations were conducted, the total energy values became more negative, with M12 showing -48.25 kcal/mol and M7 -40.13 kcal/mol. Conclusion: M12 (2-desoxypleniradin-L-|A-arabinopyranoside, 2-acetate) appears to be a promising candidate as a potential PPAR-γ inhibitor for treating type 2 diabetes.