Structure-based simulations complemented by conventional all-atom simulations to provide new insights into the folding dynamics of human telomeric G-quadruplex  

作　　者：Yun-Qiang Bian Feng Song Zan-Xia Cao Jia-Feng Yu Ji-Hua Wang 边运强;宋峰;曹赞霞;于家峰;王吉华(Shandong Key Laboratory of Biophysics,Institute of Biophysics,Dezhou University,Dezhou 253023,China)

机构地区：[1]Shandong Key Laboratory of Biophysics,Institute of Biophysics,Dezhou University,Dezhou 253023,China

出　　处：《Chinese Physics B》2021年第7期646-654,共9页中国物理B（英文版）

基　　金：the National Natural Science Foundation of China(Grant Nos.11504043,61671107,31670727,and 61771093);the Science Foundation of Shandong Province of China(Grant No.ZR2016JL027);the Taishan Young Scholars Program of Shandong Province of China(Grant No.tsqn20161049);the Youth Science and Technology Innovation Plan of Universities in Shandong,China(Grant No.2019KJE007)。

摘　　要：The hybrid atomistic structure-based model has been validated to be effective in investigation of G-quadruplex folding.In this study,we performed large-scale conventional all-atom simulations to complement the folding mechanism of human telomeric sequence Htel24 revealed by a multi-basin hybrid atomistic structure-based model.Firstly,the real time-scale of folding rate,which cannot be obtained from the structure-based simulations,was estimated directly by constructing a Markov state model.The results show that Htel24 may fold as fast as on the order of milliseconds when only considering the competition between the hybrid-1 and hybrid-2 G-quadruplex conformations.Secondly,in comparison with the results of structure-based simulations,more metastable states were identified to participate in the formation of hybrid-1 and hybrid-2 conformations.These findings suggest that coupling the hybrid atomistic structure-based model and the conventional all-atom model can provide more insights into the folding dynamics of DNA G-quadruplex.As a result,the multiscale computational framework adopted in this study may be useful to study complex processes of biomolecules involving large conformational changes.

关 键 词：molecular dynamics simulation structure-based model all-atom model DNA G-quadruplex 

分 类 号：R318[医药卫生—生物医学工程]