File(s) not publicly available
Reason: Data available on request as detailed below
Metadata supporting the article: Microsecond-timescale MD simulation of EGFR minor mutation predicts the structural flexibility of EGFR kinase core that reflects EGFR inhibitor sensitivity
Approximately 15%–30% of patients with lung cancer harbor mutations in the EGFR gene, but little is known about the characteristics, activation, and sensitivity to tyrosine kinase inhibitors for many of the identified EGFR mutations. Using binding free energy calculations and microsecond-timescale molecular dynamic simulations on the EGFR-L747P mutation, we show that this mutation considerably stabilizes the active conformation via salt-bridge formation between K745 and E762.
Data generated in this study include patient computed tomography (CT) data, half maximal inhibitory concentration (IC50) data for specified EGFR mutants, molecular dynamic simulation data and next-generation sequencing analysis data.
Data access:
EGFR mutant cell line IC50 data (excel format) and immunoblot data (tiff and jpg format) are available as Supplementary information within the related article. Further requests for these data should be made to Dr Ryohei Katayama, Japanese Foundation for Cancer Research Cancer Chemotherapy Center (ryohei.katayama@jfcr.or.jp).
Molecular dynamic simulation data are too large to be openly shared and so are only available on request from Dr Mitsugu Araki, Kyoto University (araki.mitsugu.6w@kyoto-u.ac.jp).
The following data are not publicly available to protect patient privacy:
Next-generation sequencing analysis data (fastq format) are available under controlled access from the NBDC Human Database JGAS000189 (https://humandbs.biosciencedbc.jp/en/hum0194-v1).
Patient CT Images (jpg format) are available by request from Dr Makoto Nishio, Japanese Foundation for Cancer Research (mnishio@jfcr.or.jp).
Diagnostic EGFR mutation test data are available by request from Dr Ryohei Katayama, Japanese Foundation for Cancer Research Cancer Chemotherapy Center (ryohei.katayama@jfcr.or.jp).
Study approval and patient consent:
Patients provided informed consent in writing and agreed to the use of their residual biopsy samples after disease progression. This study was performed as an approved clinical observation study by the Institutional Review Board of the Cancer Institute Hospital at Japanese Foundation for Cancer Research.
