Different Inhibitory Activity of Abemaciclib, Hymenialdisine, and Indirubin on CDK۶: A Molecular Dynamics Simulation

سال انتشار: 1399
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 419

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شناسه ملی سند علمی:

ICIBS01_026

تاریخ نمایه سازی: 2 آذر 1399

چکیده مقاله:

Introduction & Objectives: Cyclin-dependent kinase ۶ (CDK۶) is a member of cell cycle–regulating proteins that plays an important role in cancer cell growth. Some inhibitors such as Abemaciclib, Hymenialdisine, and Indirubin decrease the activity of CDK۶ and cause to cell arresting. This study aims to evaluate the effects of these inhibitors on the structure of CDK۶ using molecular dynamics (MD) simulation.Materials & Methods: The PDB file of CDK۶ was obtained from the protein data bank server (http://www.rcsb.org). Primary simulation of CDK۶ was performed by Gromacs software. Then the Molecular docking of inhibitors did on CDK۶ protein in ۲۰۰ stages using AutoDock v.۴.۲ software. The last simulation of CDK۶ in presence of inhibitors had been done after docking.Results: Indirubin had the lowest value of binding energy (BE) to bind with CDK۶. All three drugs significantly decreased the Root Mean-Square Deviation (RMSD). Hymenialdisine decreased the radius of gyration (Rg) strongly. It also decreased the coil structure of CDK۶. Variation in the α-Helix and β-Sheet structures was significantly in the presence of Indirubin and Abemaciclib.Conclusion: All three drugs reduce the activity of CDK۶. Although Hymenialdisine shows a lower tendency to bind to CDK۶ than Indirubin and Abemaciclib, it decreases the availability of the active site. Also, these three inhibitors hamper protein from its proper function through altering its secondary structures.

نویسندگان

Amir Safi

Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran

Javad Saffari-Chaleshtori

Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

Majid Asadi-Samani

Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

Korosh Ashrafi-Dehkordi

Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran