title: Molecular Docking and Molecular Dynamics to Identify a Novel Human Immunodeficiency Virus Inhibitor from Alkaloids of Toddalia asiatica.
abstract: 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.
  
  
  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 (ΔG), 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  In the present study, the molecular docking and MD simulations are performed to explore the possible binding mode of HIV 1 RT with 12 alkaloids of T. asiatica. Molecular docking by AutoDock4 revealed three alkaloids toddanol, toddanone, and toddalenone with highest binding affinity towards HIV 1 RT. The drug likeness model score revealed a positive score for toddanol and toddanone which is comparable to the drug likeness score of the standard anti HIV drug zidovudine. Results from simulation analysis revealed that toddanol RT complex is more stable than toddanone RT complex inferring toddanol as a potential anti HIV drug molecule. Abbreviations used: HIV: Human immunodeficiency virus, HIV 1 RT: HIV 1 reverse transcriptase, RNase H: Ribonuclease H, MD: Molecular dynamics, PDB: Protein databank, RMSD: Root mean square deviation, RMSF: Root mean square fluctuation.
authors.affiliation: Plant Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: R
authors.initials: R
authors.lastname: Priya
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India.
authors.forename: Rajendrarao
authors.initials: R
authors.lastname: Sumitha
authors.affiliation: Plant Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: C George Priya
authors.initials: CG
authors.lastname: Doss
authors.affiliation: Plant Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: C
authors.initials: C
authors.lastname: Rajasekaran
authors.affiliation: Plant Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: S
authors.initials: S
authors.lastname: Babu
authors.affiliation: Plant Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: R
authors.initials: R
authors.lastname: Seenivasan
authors.affiliation: Plant Biotechnology, School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu, India.
authors.forename: R
authors.initials: R
authors.lastname: Siva
keywords: Alkaloids; Autodock v4.0; drug-likeness; human immunodeficiency virus-1 reverse transcriptase; molecular dynamics simulation; molecular properties; toddanol; toddanone