Title:Docking Study on Caspase 3 Inhibitors As Potential Drugs For Traumatic
Brain Cell Apoptosis
Volume: 21
Issue: 3
Author(s): Sajad Najafi, Abbas Alibakhshi, Karim Mahnam and Javad Ranjbari*
Affiliation:
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Keywords:
Caspase 3, apoptosis, virtual screening, docking, MD simulation, MM/PBSA binding free energy.
Abstract: Background: Apoptosis of brain cells (neurons and glia) has a crucial role in humans' pathology
of traumatic brain injury (TBI). So, a decrease in the apoptosis rate can potentially reduce the harmful
effects and lead to better functional outcomes. Drug repurposing by computational methodologies like
protein-ligand docking allows us to make drug discovery more efficient and less expensive.
Objective: In the current study, we used the methodology to study the inhibitory effect of thousands of
FDA/non-FDA approved, investigational compounds on caspase 3 as one of the most important members
of the cell apoptosis pathway.
Methods: Molecular docking and pharmacokinetic properties calculations were done. The molecular dynamics
(MD) simulations of all complexes and free caspase 3 were carried out. We carried out docking
experiments using in silico methods and docked a pool of medications to the active site of the human
caspase-3 X-ray structure. The best compounds were selected and subjected to pharmacokinetic analysis,
molecular simulation, and free energy calculations.
Results: Finally, 6 components (Naldemedine, Celastrol, Nilotinib, Drospirenone, Lumacaftor, and R-
343) were selected as the best in terms of structural and pharmaceutical properties, low toxicity that can
be administered orally for the preclinical and clinical future investigations.
