折叠(DSP实现)
循环(图论)
混合器
动力学
圆二色性
蛋白质折叠
化学物理
结晶学
化学
生物物理学
材料科学
纳米技术
物理
核磁共振
生物
微流控
工程类
电气工程
组合数学
量子力学
数学
作者
Zheyu Li,Rui Hu,Tao Li,Jiang Zhu,Huijuan You,Yiwei Li,Bi‐Feng Liu,Conggang Li,Ying Li,Yunhuang Yang
标识
DOI:10.1073/pnas.2315401121
摘要
Biomacromolecular folding kinetics involves fast folding events and broad timescales. Current techniques face limitations in either the required time resolution or the observation window. In this study, we developed the TeZla micromixer, integrating Tesla and Zigzag microstructures with a multistage velocity descending strategy. TeZla achieves a significant short mixing dead time (40 µs) and a wide time window covering four orders of magnitude (up to 300 ms). Using this unique micromixer, we explored the folding landscape of c-Myc G4 and its noncanonical-G4 derivatives with different loop lengths or G-vacancy sites. Our findings revealed that c-Myc can bypass folding intermediates and directly adopt a G4 structure in the cation-deficient buffer. Moreover, we found that the loop length and specific G-vacancy site could affect the folding pathway and significantly slow down the folding rates. These results were also cross-validated with real-time NMR and circular dichroism. In conclusion, TeZla represents a versatile tool for studying biomolecular folding kinetics, and our findings may ultimately contribute to the design of drugs targeting G4 structures.
科研通智能强力驱动
Strongly Powered by AbleSci AI