title: Virtual screening of natural compounds as inhibitors of EGFR 696-1022 T790M associated with non-small cell lung cancer.
abstract: Non-small cell lung cancer (NSCLC) is the most dominating and lethal type of lung cancer triggering more than 1.3 million deaths per year. The most effective line of treatment against NSCLC is to target epidermal growth factor receptor (EGFR) activating mutation. The present study aims to identify the novel anti-lung cancer compounds form nature against EGFR 696-1022 T790M by using in silico approaches. A library of 419 compounds from several natural resources was subjected to pre-screen through machine learning model using Random Forest classifier resulting 63 screened molecules with active potential. These molecules were further screened by molecular docking against the active site of EGFR 696-1022 T790M protein using AutoDock Vina followed by rescoring using X-Score. As a result 4 compounds were finally screened namely Granulatimide, Danorubicin, Penicinoline and Austocystin D with lowest binding energy which were -6.5 kcal/mol, -6.1 kcal/mol, -6.3 kcal/mol and -7.1 kcal/mol respectively. The drug likeness of the screened compounds was evaluated using FaF-Drug3 server. Finally toxicity of the hit compounds was predicted in cell line using the CLC-Pred server where their cytotoxic ability against various lung cancer cell lines was confirmed. We have shown 4 potential compounds, which could be further exploited as efficient drug candidates against lung cancer.
authors.affiliation: Department of Biotechnology, Kumaun University, Bhimtal Campus Bhimtal, Uttarakhand, India.
authors.forename: Mahesha
authors.initials: M
authors.lastname: Nand
authors.affiliation: Department of Botany, Kumaun University, S.S.J Campus, Almora, Uttarakhand, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Maiti
authors.affiliation: Department of Biotechnology, Kumaun University, Bhimtal Campus Bhimtal, Uttarakhand, India.
authors.forename: Ragini
authors.initials: R
authors.lastname: Pant
authors.affiliation: Department of Information Technology, Kumaun University, SSJ Campus, Almora, Uttarakhand 263601, India.
authors.forename: Madhulata
authors.initials: M
authors.lastname: Kumari
authors.affiliation: Department of Botany, Kumaun University, S.S.J Campus, Almora, Uttarakhand, India.
authors.forename: Subhash
authors.initials: S
authors.lastname: Chandra
authors.affiliation: Department of Biotechnology, Kumaun University, Bhimtal Campus Bhimtal, Uttarakhand, India.
authors.forename: Veena
authors.initials: V
authors.lastname: Pande
keywords: EGFR; lung cancer; machine learning; molecular docking; natural compounds; prediction