Molecular docking and molecular dynamic studies: screening of phytochemicals against EGFR, HER2, estrogen and NF-KB receptors for their potential use in breast cancer

Abstract

Breast cancer (BC) is a second common malignancy in female globally. Hence, identification of novel therapeutic agents is extremely important. Molecular docking and MD simulation are the important tools in the process of drug discovery for searching the potential hits. The structure-based drug designing technique also reveals the information about ligands behavior in computational environment. Docking tools help in visualization and analysis of protein–ligand complex at atomic level. Molecular dynamics shows the stability of the molecules in the receptor cavity in the simulated environment. In this research work, we have screened potent phytochemicals against the BC. We docked the phytochemicals and examined the binding affinities of ligands towards the EGFR, HER2, estrogen and NF-κB receptors. Pristimerin, ixocarpalactone A, viscosalactone B and zhankuic acid A have shown higher binding affinities and energies towards targeted receptors among the screened phytochemicals. MD simulation study shows stability of docked complex for pristimerin and HER2 receptor. These phytochemicals can be repurposed for their anticancer activity. This in-silico work provides a strong ground for further investigation of their anticancer activity.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

Keywords:

• Breast cancer
• EGFR
• HER2
• estrogen receptor
• NF-κB receptors
• molecular docking
• molecular dynamics
• phytochemicals

Acknowledgements

The authors are thankful to ICMR, Govt. of India, New Delhi for providing financial support on breast cancer research. We are highly indebted to our university, Rajiv Gandhi University of Health Sciences, Karnataka for providing cloud facility and for access of databases, journals. Authors grateful to Sri. B.Premnath Reddy, Chairman, Acharya Institutes, for his support. We would like to thank Principal of Acharya & BM Reddy College of Pharmacy, Bengaluru and other management staff for guidance and support. Lastly, we are thankful to Director, CSIR-NEIST,all SRTP team, eminent scientists, and mentors for constant encouragements in summer research training program 2020.

Disclosure statement

All authors declare that there is a no conflict of interest, financial or otherwise.

Additional information

Funding

This study was financially supported by provided by Indian Council of Medicinal Research (ICMR), Govt. of India, New Delhi, Grand no: (BIC/12(06)/2015)