Molecular docking studies of Traditional Chinese Medicinal compounds against known protein targets to treat non-small cell lung carcinomas.
In silico drug design using virtual screening, absorption, distribution, metabolism and excretion (ADME)/Tox data analysis, automated docking and molecular dynamics simulations for the determination of lead compounds for further in vitro analysis is a cost effective strategy. The present study used this strategy to discover novel lead compounds from an in-house database of Traditional Chinese Medicinal (TCM) compounds against epithelial growth factor receptor (EGFR) protein for targeting non-small cell lung cancer (NSCLC). After virtual screening of an initial dataset of 2,242 TCM compounds, leads were identified based on binding energy and ADME/Tox data and subjected to automated docking followed by molecular dynamics simulation. Triptolide, a top compound identified by this vigorous in silico screening, was then tested in vitro on the H2347 cell line carrying wild-type EGFR, revealing an anti-proliferative potency similar to that of known drugs against NSCLC.
Department of Cardiothoracic Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China.
Guo-Fang
GF
Zhao
Department of Stem Cell Laboratory, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China.
Zuo-An
ZA
Huang
Department of Cardiothoracic Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China.
Xue-Kui
XK
Du
Department of Cardiothoracic Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China.
Ming-Lei
ML
Yang
Department of Stem Cell Laboratory, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China.
Dan-Dan
DD
Huang
Department of Stem Cell Laboratory, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China.
Shun
S
Zhang
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D003198:Computer Simulation; D015195:Drug Design; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008175:Lung Neoplasms; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D066246:ErbB Receptors