Virtual high throughput screening of natural peptides against ErbB1 and ErbB2 to identify potential inhibitors for cancer chemotherapy.
Sunil Kumar PatnaikSelvaraj AyyamperumalDhananjay JadeNagarjuna PalathotiKrishna Swaroop AkeySrikanth JupudiMichael A HarrisonSreenivasan PonnambalamNanjan MjMoola Joghee Nanjan ChandrasekarPublished in: Journal of biomolecular structure & dynamics (2023)
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.
Keyphrases
- tyrosine kinase
- epidermal growth factor receptor
- poor prognosis
- cell proliferation
- growth factor
- endothelial cells
- long non coding rna
- squamous cell carcinoma
- radiation therapy
- risk assessment
- molecular docking
- climate change
- childhood cancer
- transcription factor
- binding protein
- vascular endothelial growth factor
- wound healing
- lymph node metastasis