Structure-based virtual screening, pharmacokinetic prediction, molecular dynamics studies for the identification of novel EGFR inhibitors in breast cancer
- Title
- Structure-based virtual screening, pharmacokinetic prediction, molecular dynamics studies for the identification of novel EGFR inhibitors in breast cancer
- Creator
- Anbuselvam M.; Easwaran M.; Meyyazhagan A.; Anbuselvam J.; Bhotla H.K.; Sivasubramanian M.; Annadurai Y.; Kaul T.; Pappusamy M.; Balasubramanian B.
- Description
- Breast cancer is one of the most prevalent malignancy cancer types especially affecting women globally. EGFR is a proto onco gene as well as the first identified tyrosine kinase receptor. It plays a dynamic role in many biological tasks such as apoptosis, cell cycle progression, differentiation, development and transcription. Somatic mutation in the EGFR kinase domain derails the normal kinase activity and over expression leads to the progression of cancer especially breast cancer. EGFR is one of the well-known therapeutic targets for breast cancer. In this scenario, we attempt to identify novel potent inhibitors of EGFR. Initially, we performed structure-based virtual screening and identified four potential compounds effective against EGFR. Further, the compounds were subjected to ADME prediction as part of evaluation of the druggability and all the four compounds found to fall under satisfactory range with predicted pharmacokinetic properties. Eventually, the conformational stability of proteinligand complex was analyzed at different time scale by using Gromacs software. Molecular dynamics simulation run of 20 ns is carried out and results were analyzed using root mean square deviation (RMSD), root mean square fluctuation (RMSF) to signify the stability of proteinigand complex. The stability of the proteinligand complex is more stable throughout entire simulation. From the results obtained from in silico studies, we propose that these compounds are exceptionally useful for further lead optimization and drug development. Communicated by Ramaswamy H. Sarma. 2020 Informa UK Limited, trading as Taylor & Francis Group.
- Source
- Journal of Biomolecular Structure and Dynamics, Vol-39, No. 12, pp. 4462-4471.
- Date
- 2021-01-01
- Publisher
- Taylor and Francis Ltd.
- Subject
- Breast cancer; EGFR; molecular dynamics simulation; virtual screening
- Coverage
- Anbuselvam M., Department of Biotechnology, Selvamm College of Arts and Science (Autonomous), Namakkal, India; Easwaran M., Nutritional Improvement of Crops International Centre for Genetic Engineering and Biotechnology, New Delhi, India; Meyyazhagan A., Euroespes Biomedical Research Center, Corunna, Spain; Anbuselvam J., Department of Animal Science, Bharathidasan University, Tiruchirappalli, India; Bhotla H.K., Department of Medicine, University of Perugia, Perugia, Italy; Sivasubramanian M., Department of Social Science, Vellore Institute of Technology, Vellore, India; Annadurai Y., Department of Animal Science, Bharathidasan University, Tiruchirappalli, India; Kaul T., Nutritional Improvement of Crops International Centre for Genetic Engineering and Biotechnology, New Delhi, India; Pappusamy M., School of Life Science, Christ University, Bengaluru, India; Balasubramanian B., Department of Food Science and Biotechnology, Sejong University, Seoul, South Korea
- Rights
- Restricted Access
- Relation
- ISSN: 7391102; PubMed ID: 32567493; CODEN: JBSDD
- Format
- Online
- Language
- English
- Type
- Article
Collection
Citation
Anbuselvam M.; Easwaran M.; Meyyazhagan A.; Anbuselvam J.; Bhotla H.K.; Sivasubramanian M.; Annadurai Y.; Kaul T.; Pappusamy M.; Balasubramanian B., “Structure-based virtual screening, pharmacokinetic prediction, molecular dynamics studies for the identification of novel EGFR inhibitors in breast cancer,” CHRIST (Deemed To Be University) Institutional Repository, accessed February 25, 2025, https://archives.christuniversity.in/items/show/16072.