Document Type : Original Article
Authors
- Arian Ahadi 1
- Tooba Abdizadeh 1
- Alireza Bakhtiari 1
- Maryam Momeni zade 2
- Mohammad Nikbakht 3
- Javad Saffari-Chaleshtori 1, 4
1 Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
2 Medical plants, Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
3 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
4 Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Background: Berberine is an alkaloid that exists in barberry with many different antioxidant and pharmaceutical effects. This simulation study investigated the effect of Berberine on cyclin-dependent kinases (CDKs) which are important Serine/threonine kinase proteins involved in control of the cell cycle.
Methods: The three-dimensional structure of Berberine was obtained from the PubChem server and then converted to the PDB file by Avogadro software. The PDB files of CDK2, 4, and 6 were obtained from the RCSB server. Autodock v.4.2.6 software was used for docking the Berberine into the CDKs at the 200 independent runs. The molecular dynamic Gromacs 2022 software was used to investigate of molecular dynamin properties of CDKs and CDKs-Berberine complexes individually. The simulation system was performed at 50 nanoseconds using the G43A1 force field and the SPC216 model.
Results: Berberine bonded to the CDKs with high affinity and low inhibition constant. The binding of Berberine into the CDK6 was at the Ile19, Val27, and Lys43 amino acid residues that are involved at the ATP binding site of CDK6 by 7.07 kcal/mol and 6.58 ki. The molecular dynamic investigations confirmed the stability of these bindings and structural changes on the CDK6 after docking the Berberine.
Conclusion: Berberine can bind to the ATP binding site of CDK6 with high affinity and prevents ATP binding. This competitive inhibition prevents the ATP from binding at the ATP binding site of CDK6. This can lead to an arrest in the G1/S phase of the cell cycle.
Highlights
Arian Ahadi (Google Scholar) (PubMed)
Javad Saffari-Chaleshtori (Google Scholar) (PubMed)
Keywords
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