Department of Physics, Department of Biochemistry, and Informatics Institute and ‡Department of Biochemistry, University of Missouri , Columbia, Missouri 65211, United States.
J Phys Chem B. 2017 Aug 31;121(34):8026-8036. doi: 10.1021/acs.jpcb.7b03873. Epub 2017 Aug 21.
We develop a partial charge-based tightly bound ion (PCTBI) model for the ion effects in RNA folding. On the basis of the Monte Carlo tightly bound ion (MCTBI) approach, the model can account for ion fluctuation and correlation effects, and can predict the ion distribution around the RNA. Furthermore, unlike the previous coarse-grained RNA charge models, where negative charges are placed on the phosphates only, the current new model considers the detailed all-atom partial charge distribution on the RNA. Thus, the model not only keeps the advantage of the MCTBI model, but also has the potential to provide important detailed information unattainable by the previous MCTBI models. For example, the model predicts the reduction in ion binding upon protein binding and ion-induced conformational switches. For hepatitis C virus genomic RNA, the model predicts a Mg-induced stabilization of a kissing motif for a cis-acting regulatory element in the genomic RNA. Extensive theory-experiment comparisons support the reliability of the theoretical predictions. Therefore, the model may serve as a robust starting point for further development of an accurate method for ion effects in an RNA conformational equilibrium and RNA-cofactor interactions.
我们开发了一种基于部分电荷的紧束缚离子 (PCTBI) 模型，用于研究 RNA 折叠中的离子效应。该模型基于蒙特卡罗紧束缚离子 (MCTBI) 方法，可以考虑离子波动和相关效应，并预测 RNA 周围的离子分布。此外，与之前的粗粒 RNA 电荷模型不同，后者仅在磷酸上放置负电荷，而当前的新模型考虑了 RNA 上详细的全原子部分电荷分布。因此，该模型不仅保留了 MCTBI 模型的优势，而且还有潜力提供以前的 MCTBI 模型无法获得的重要详细信息。例如，该模型预测了在与蛋白质结合时离子结合减少以及离子诱导的构象开关。对于丙型肝炎病毒基因组 RNA，该模型预测了镁诱导的顺式作用调节元件中“亲吻”基序的稳定化。广泛的理论与实验比较支持了理论预测的可靠性。因此，该模型可能成为进一步开发 RNA 构象平衡和 RNA-辅助因子相互作用中离子效应的准确方法的稳健起点。
