Virtual high throughput screening of natural peptides against ErbB1 and ErbB2 to identify potential inhibitors for cancer chemotherapy

Abstract

Human epidermal growth factor receptors (EGFR), namely ErbB1/HER1, ErbB2/HER2/neu, ErbB3/HER3, and ErbB4/HER4, the trans-membrane family of tyrosine kinase receptors, are overexpressed in many types of cancers. These receptors play an important role in cell proliferation, differentiation, invasion, metastasis and angiogenesis including unregulated activation of cancer cells. Overexpression of ErbB1 and ErbB2 that occurs in several types of cancers is associated with poor prognosis leading to resistance to ErbB1-directed therapies. In this connection, promising strategy to overcome the disadvantages of the existing chemotherapeutic drugs is the use of short peptides as anticancer agents. In the present study, we have performed virtual high throughput screening of natural peptides against ErbB1 and ErbB2 to identify potential dual inhibitors and identified five inhibitors based on their binding affinities, ADMET analysis, MD simulation studies and calculation of free energy of binding. These natural peptides could be further exploited for developing drugs for treating cancer.

Communicated by Ramaswamy H. Sarma

Keywords:

• Drug discovery
• anticancer peptides
• dual targeting
• vHTS
• ADME TOPKAT
• MM-PBSA
• peptide therapeutics

Acknowledgments

Authors expresses their immense gratitude to JSS College of Pharmacy Ooty, JSS Academy of Higher Education and Research, Mysuru, and School of Life Sciences, JSS Academy of Higher Education & Research (Ooty Campus), Longwood, Mysuru Road, Ooty-643001, Tamilnadu, India and School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK for the facilities offered.

Disclosure statement

The authors declare that they have no conflict of interests.

Ethical approval

Not Required

Data availability statement

All data generated and analyzed during this study are included within this article and supplementary information submitted to the journal.

Funding

No funding was provided for the above mentioned research manuscript

Author contributions

Conceptualization, methodology, software, validation, formal analysis, data curation: Sunil Kumar Patnaik, Selvaraj Ayyamperumal, Dhananjay Jade; writing-original draft preparation: Sunil Kumar Patnaik, Selvaraj Ayyamperumal, Palathoti Nagarjuna, Akey Krishna Swaroop, Jupudi Srikanth; review, editing and supervision: Moola Joghee Nanjan, Moola Joghee Nanjan Chandrasekar, Michael A. Harrison, Sreenivasan Ponnambalam.