Evaluating the Effects of Molecular Dynamic And Docking of Abemaciclib, Hymenialdisine, and Indirubin on CDK-2 Inhibition by Simulation Study

• Published in: Majallah-i dānishgāh-i ʻulūm-i pizishkī-i Ardabīl Vol. 22; no. 1; pp. 39 - 49
• Main Authors: Asadi-Samani, Majid, Jamali, Navid, Saffari-Chaleshtori, Javad, Ashrafi-Dehkordi, Korosh
• Format: Journal Article
• Language: Persian
• Published: Ardabil University of Medical Sciences 01.03.2022
• Subjects: abemaciclib; cdk-2; hymenialdisin; indirubin; molecular dynamic simulation
• ISSN: 2228-7280; 2228-7299
• DOI: 10.52547/jarums.22.1.39

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.