Evaluation of Potential EGFR Inhibitors for Non-small Cell Lung Cancer: A Structure-based Virtual Screening and Molecular Dynamics Study
Gobalan Krishnasamy
Department of Biotechnology, Jamal Mohamed College, Trichy, Tamil Nadu, India.
Sudharsan Parthasarathy
Department of Forestry, Nagaland University (Hqrs.), Lumami, Nagaland, India.
Shalini Rajasekaran
Department of Biotechnology, Jamal Mohamed College, Trichy, Tamil Nadu, India.
T. William Raja
Department of Biotechnology, Bishop Heber College, Tiruchirappalli, Tamil Nadu, India.
S. Geet Andrea
Department of Biotechnology, Jamal Mohamed College, Trichy, Tamil Nadu, India.
Siva Vijayakumar Tharumasivam *
Department of Biotechnology, Dhanalakshmi Srinivasan University, Samayapuram, Tiruchirappalli, Tamil Nadu, India.
*Author to whom correspondence should be addressed.
Abstract
Non-small cell lung cancer is a leading cause of cancer deaths globally. EGFR is one of the attractive drug targets for non small cell lung cancer. It was first identified receptor tyrosine kinase receptor. It plays a critical role in the variety of biological activity apoptosis, cell cycle progression, differentiation, development, and transcription. Somatic mutation occurs in human EGFR. After that the normal function of EGFR was over expressed can leads to develop lung cancer. In this study we have identified three potential compounds using structure based virtual screening. Then thus compounds were evaluated ADME properties, all the compounds are under acceptable range with predicted ADME properties, then thus protein-ligand complex stability were carried out using Gromacs. The stability of the protein-ligand complex is stable throughout entire simulation, especially MET 769 is significant for stability of the complex. Furthermore, invitro cytotoxicity assay were performed for the best one compounds against non small cell lung cancer cell line.
Keywords: EGFR, virtual screening, molecular dynamics simulation, In vitro cytotoxicity