Search for potentially biased epidermal growth factor receptor (EGFR) inhibitors through pharmacophore modelling, molecular docking, and molecular dynamics (MD) simulation approaches

Epidermal growth factor receptor (EGFR), being one of the most crucial receptor in cancer therapy, has been selected as a potential target for the present study. Ligand-based pharmacophore model (n = 30, R2=0.93 with root mean square deviation = 1.14, ΔCost = 144.27 and configuration cost = 21) was developed and validated with Fischer’s randomisation (at 95% confidence), test set (n = 225, R2 pred = 0.81), external data set (n = 13, R2 pred = 0.95) and decoy set (n = 70), further the model has been used to search for novel EGFR inhibitors. The validated model was used for virtual screening of zinc database. A pool of 115,948 candidate molecules was screened through the model. Subsequently, molecules having predicted IC50 Communicated by Ramaswamy H. Sarma