Background: Cyclin-Dependent Kinases-6 (CDK-6) is a serine/threonine protein kinase
with regular activity in the cell cycle. Some inhibitors, such as abemaciclib, hymenialdisine, and indirubin,
cause cell arrest by decreasing its activity.
Objectives: The purpose of this study was to evaluate the Molecular Dynamic (MD) effects of abemaciclib,
hymenialdisine, and indirubin on the structure of CDK-6.
Methods: The PDB file of CDK-6 was obtained from the Protein Data Bank (http://www.rcsb.org).
After the simulation of CDK-6 in the Gromacs software, 200 stages of molecular docking were run
on CDK-6 in the presence of the inhibitors using AutoDock 4.2. The simulation of CDK-6 in the
presence of inhibitors was performed after docking.
Results: Abemaciclib showed the greatest tendency to bind CDK-6 via binding 16 residues in the
binding site with hydrogen bonds and hydrophobic bonding. CDK-6 docked to hymenialdisine and
indirubin increased the Total Energy (TE) and decreased the radius of gyration (Rg). CDK-6 docked
to hymenialdisine significantly decreased the coil secondary structure.
Conclusion: CDK-6 is inhibited via high binding affinity to abemaciclib, hymenialdisine, and indirubin
inhibitors and induces variation in the secondary structure and Rg in the CDK-6 docked to the
three inhibitors. It seems that developing a drug with a binding tendency to CDK6 that is similar to
those of abemaciclib, indirubin, and hymenialdisine can change the secondary structure of CDK6,
possibly more potently, and can be used to develop anticancer drugs. However, additional studies
are needed to confirm this argument.