IDENTIFICATION OF POTENTIAL INHIBITORS OF EPIDERMAL GROWTH FACTOR RECEPTOR TYROSINE KINASE BY VIRTUAL SCREENING AND DOCKING STUDIESAbstract
Understanding the mode of inhibition through the crystal structures of EGFR kinase domain complex with small molecule inhibitors provides us to search for potential ligands of EGFR. The binding mode analysis of pyridopyrimidine analog reveals that the presence of hydrogen bonds between the target protein amino acid Met 793 (i.e. the hinge region which is responsible for catalytic activity of the domain) and the ring nitrogen of the small molecule inhibitor. In addition, amino acid Asp 855 and Lys 745 were also involved in the interaction. The present work focuses on the identification of novel ligands through computational approach. By screening of pubchem database compounds, based on the bioactive and structural similarity of a pyridopyrimidine derivative (highly potent inhibitor of EGFR), 117 compounds were identified and all are having kinase inhibition activity but were not analyzed in EGFR. Using GLIDE software, the docking was done and complete analysis of the binding mode results in eleven compounds having same pattern of interactions and these compounds may be further analyzed by in vitro for their EGFR kinase inhibition activity.
S. Sugunakala and S. Selvaraj *
Department of Bioinformatics, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.
26 August, 2016
28 October, 2016
05 November, 2016
01 March, 2017