title: In silico analysis of the effect of mutation on epidermal growth factor receptor in non-small-cell lung carcinoma: from mutational analysis to drug designing.
abstract: Tyrosine kinase inhibitors (TKI)-resistant mutation in epidermal growth factor receptor's (EGFR) kinase domain is an important anomaly to look into. Studying the mutations at atomic level using molecular dynamics simulations gave us an insight into the architectural changes happening at the microscopic level. The knowledge was used to design new TKI whose function is devoid of the affect of the mutations in kinase domain. Traditional Chinese medicinal library was used for structure-based drug designing, where virtual screening was followed by ADME/Tox analysis and the shortlisted compounds were docked into the kinase domain of EGFR and simulated there using atomic-level selection of the grid. The shortlisted compounds from molecular docking analysis were subjected to MM-PBSA calculations. The in silico data generated is giving a strong lead compound for further in vitro and in vivo analysis.
authors.affiliation: a The First Department of Oncology Subject , Center Hospital of Zhumadian in Henan , Zhumadian , Henan 463000 , P.R. China.
authors.forename: Fu-Li
authors.initials: FL
authors.lastname: Zhao
authors.affiliation: a The First Department of Oncology Subject , Center Hospital of Zhumadian in Henan , Zhumadian , Henan 463000 , P.R. China.
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Yang
authors.affiliation: a The First Department of Oncology Subject , Center Hospital of Zhumadian in Henan , Zhumadian , Henan 463000 , P.R. China.
authors.forename: Sen
authors.initials: S
authors.lastname: Xiang
authors.affiliation: a The First Department of Oncology Subject , Center Hospital of Zhumadian in Henan , Zhumadian , Henan 463000 , P.R. China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Gao
authors.affiliation: a The First Department of Oncology Subject , Center Hospital of Zhumadian in Henan , Zhumadian , Henan 463000 , P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000595:Amino Acid Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D006860:Hydrogen Bonding; D008175:Lung Neoplasms / Q000235:genetics; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: MM-PBSA; NSCLC; docking; lung cancer; mutation; simulations