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Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X+S768I mutations in non-small cell lung cancer: An in silico approaches 期刊论文

编号：

28D8451BF080E0C4DA84986738E20D32
作者：

Wang, JunLing#^[2]Liu, MingSheng(刘明生)#^[3]Fu, YuDong^[4];Kan, QiangBo^[4];Li, ChunYan^[5];Ma, Rong^[2];Fang, ZheWei^[2];Liu, HongXia^[2];Li, MengXian^[2];Lv, JiaLing^[5];Sang, Peng^[6];Zhang, Chao(张超)*^[1]Li, HongWei(李宏伟)*^[1]
语种：

英文
期刊：

OPEN LIFE SCIENCES ISSN：2391-5412 2023 年 18 卷 1 期 ; NOV 27
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关键词：

epidermal growth factor receptor G719X and S768I mutations non-small cell lung cancer molecular dynamics simulation conformation free energy landscape
摘要：

Non-small cell lung cancer (NSCLC) is often driven by mutations in the epidermal growth factor receptor (EGFR) gene. However, rare mutations such as G719X and S768I lack standard anti-EGFR targeted therapies. Understanding the structural differences between wild-type EGFR and these rare mutants is crucial for developing EGFR-targeted drugs. We performed a systematic analysis using molecular dynamics simulations, essential dynamics (ED), molecular mechanics Poisson-Boltzmann surface area, and free energy calculation methods to compare the kinetic properties, molecular motion, and free energy distribution between wild-type EGFR and the rare mutants'' structures G719X-EGFR, S768I-EGFR, and G719X + S768I-EGFR. Our results showed that S768I-EGFR and G719X + S768I-EGFR have higher global and local conformational flexibility and lower thermal and global structural stability than WT-EGFR. ED analysis revealed different molecular motion patterns between S768I-EGFR, G719X + S768I-EGFR, and WT-EGFR. The A-loop and alpha C-helix, crucial structural elements related to the active state, showed a tendency toward active state development, providing a molecular mechanism explanation for NSCLC caused by EGFR S768I and EGFR G719C + S768I mutations. The present study may be helpful in the development of new EGFR-targeted drugs based on the structure of rare mutations. Our findings may aid in developing new targeted treatments for patients with EGFR S768I and EGFR G719X + S768I mutations.
推荐引用方式
GB/T 7714：

Wang Jun-Ling,Liu Ming-Sheng,Fu Yu-Dong, et al. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X+S768I mutations in non-small cell lung cancer: An in silico approaches [J].OPEN LIFE SCIENCES,2023,18(1).
APA：

Wang Jun-Ling,Liu Ming-Sheng,Fu Yu-Dong,Kan Qiang-Bo,&Li Hong-Wei.(2023).Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X+S768I mutations in non-small cell lung cancer: An in silico approaches .OPEN LIFE SCIENCES,18(1).
MLA：

Wang Jun-Ling, et al. "Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X+S768I mutations in non-small cell lung cancer: An in silico approaches" .OPEN LIFE SCIENCES 18,1(2023).
入库时间：

2023/12/23 21:39:45
更新时间：

2023/12/23 21:39:45
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