Computational study on the binding of Mango-II RNA aptamer and fluorogen using the polarizable force field AMOEBA.
Computational study on the binding of Mango-II RNA aptamer and fluorogen using the polarizable force field AMOEBA.
复制标题
DOI：
10.3389/fmolb.2022.946708
复制
发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
荧光发光适配子是一种性能良好的生物传感器，用于细胞成像和检测不同的感兴趣目标，包括RNA、非核酸分子、金属离子等。它们可以很容易地设计，一旦与特定的荧光素结合，就会发出强烈的荧光信号。最近，一种独特的适体Mango-II被发现与1-生物素和3-生物素的荧光素具有很强的亲和力和优异的荧光性能。为了探索结合机制，进行了计算模拟，以获得原子分辨率下的襟翼的结构和热力学信息。本工作利用阿米巴极化力场处理高电荷态和柔性的RNA体系，模拟了Mango-II与to1-Biotin和to3-Biotin的相互作用。用已发表的晶体结构计算的结合自由能与实验值符合得很好。考虑到对复杂RNA动力学建模的挑战，我们的工作表明，使用可极化力场的MD模拟对于理解适配子与荧光素的结合以及潜在地设计性能更好的新的适配子或荧光素是有价值的。
Fluorescent light-up aptamers (FLAPs) are well-performed biosensors for cellular imaging and the detection of different targets of interest, including RNA, non-nucleic acid molecules, metal ions, and so on. They could be easily designed and emit a strong fluorescence signal once bound to specified fluorogens. Recently, one unique aptamer called Mango-II has been discovered to possess a strong affinity and excellent fluorescent properties with fluorogens TO1-Biotin and TO3-Biotin. To explore the binding mechanisms, computational simulations have been performed to obtain structural and thermodynamic information about FLAPs at atomic resolution. AMOEBA polarizable force field, with the capability of handling the highly charged and flexible RNA system, was utilized for the simulation of Mango-II with TO1-Biotin and TO3-Biotin in this work. The calculated binding free energy using published crystal structures is in excellent agreement with the experimental values. Given the challenges in modeling complex RNA dynamics, our work demonstrates that MD simulation with a polarizable force field is valuable for understanding aptamer-fluorogen binding and potentially designing new aptamers or fluorogens with better performance.
登录
查看更多内容
影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
DOI：
10.1126/science.1207339
发表时间：
2011-07-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Paige JS;Wu KY;Jaffrey SR
通讯作者：
Jaffrey SR
影响因子：
14.9
作者：
Autour A;Westhof E;Ryckelynck M
通讯作者：
Ryckelynck M
DOI：
10.1039/c6cp02509a
发表时间：
2016-11-09
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Bell DR;Qi R;Jing Z;Xiang JY;Mejias C;Schnieders MJ;Ponder JW;Ren P
通讯作者：
Ren P
影响因子：
15
作者：
Hamelberg, D;McCammon, JA
通讯作者：
McCammon, JA