Molecular Docking and Molecular Dynamics to Identify a Novel Human Immunodeficiency Virus Inhibitor from Alkaloids of Toddalia asiatica

Background: Acquired immunodeficiency syndrome caused by human immunodeficiency virus (HIV) is an immunosuppressive disease. Over the past decades, it has plagued human health due to the grave consequences in its harness. Objective: For this reason, anti‑HIV agents are imperative, and the search for the same from natural resources would assure the safety. Materials and Methods: In this investigation we have performed molecular docking, molecular property prediction, drug‑likeness score, and molecular dynamics (MD) simulation to develop a novel anti‑HIV drug. We have screened 12 alkaloids from a medicinal plant Toddalia asiatica for its probabilistic binding with the active site of the HIV‑1‑reverse transcriptase (HIV‑1‑RT) domain (the major contributor to the onset of the disease). Results: The docking results were evaluated based on free energies of binding (∆G), and the results suggested toddanol, toddanone, and toddalenone to be potent inhibitors of HIV‑1‑RT. In addition, the alkaloids were subjected to molecular property prediction analysis. Toddanol and toddanone with more rotatable bonds were found to have a drug‑likeness score of 0.23 and 0.11, respectively. These scores were comparable with the standard anti‑HIV drug zidovudine with a model score 0.28. Finally, two characteristic protein‑ligand complexes were exposed to MD simulation to determine the stability of the predicted conformations. Conclusion: The toddanol‑RT complex showed higher stability and stronger H‑bonds than toddanone‑RT complex. Based on these observations, we firmly believe that the alkaloid toddanol could aid in efficient HIV‑1 drug discovery.