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Evaluating the Effects of Molecular Dynamic And Docking of Abemaciclib, Hymenialdisine, and Indirubin on CDK-2 Inhibition by Simulation Study
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Majid Asadi-Samani    , Navid Jamali , Javad Saffari-Chaleshtori * , Korosh Ashrafi-Dehkordi |
| Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran , j_saffari@gmail.com |
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Abstract: (642 Views) |
Background & objectives: Cyclin-dependent kinase 2 (CDK-2) is a serine/threonine protein kinase with regulatory activity in the cell cycle. Inhibitors of this protein are the treatment of choice for a variety of cancers by stopping the cell cycle. In this in silico study, the effects of docking and molecular dynamics of Abemaciclib, Hymenialdisine, and Indirubin on the inhibition of CDK-2 as one of the most important factors in the cell cycle have been investigated.
Methods: PDB file of CDK-2 protein as well as three-dimensional structures of Abemaciclib, Hymenialdisine, and Indirubin were obtained from the protein database (http://www.rcsb.org) and pubchem server, respectively. After simulating CDK-2 in Gromacs software, molecular docking of compounds on CDK-2 was performed by AutoDock 4.2 software. Finally, the most important molecular dynamics factors such as RMSD,the radius of gyration and total energy in the pre-docking state were analyzed and compared to these factors in the post-docking stage.
Results: Abemaciclib has the highest affinity for binding to amino acids at the CDK-2 binding site by releasing binding energy equivalent to 8.23 kJ/mol. The binding of Abemaciclib, Hymenialdisine, and Indirubin to CDK-2, resulted in significant reductions in some molecular dynamics factors such as mean total energy, the radius of gyration, RMSD, and changes in CDK-2 secondary structure.
Conclusion: Abemaciclib, Hymenialdisine, and Indirubin have a high tendency to interact with CDK-2, and this binding can induce significant dynamic molecular changes in the structure of CDK-2 molecule. Based on the results of molecular dynamics simulation, the secondary structure of CDK-2 changes after each ligand binds to it and makes the complex of ligand and protein more stable. |
Article number: 4 |
| Keywords: CDK-2, Abemaciclib, Hymenialdisin, Indirubin, Molecular Dynamic Simulation |
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Full-Text [PDF 849 kb]
(502 Downloads)
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Type of Study: article |
Subject:
Biochemistry
Received: 2022/05/5 | Accepted: 2022/09/5 | Published: 2022/10/2
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