增强采样与冷冻电镜数据解析镁离子与RNA的结合
Enhanced sampling and cryo-EM data resolve magnesium binding to RNA
AI总结：
研究镁离子与RNA结合难的问题，采用增强采样策略，结合势垒平坦化偏差与哈密顿量副本交换加速Mg²⁺内壳层结合，利用冷冻电镜图谱验证并引入局部分析框架，凸显采样在建模中的作用，提供模拟与实验数据整合策略。
摘要：
镁离子对RNA结构至关重要，但因其缓慢的结合动力学和实验限制难以建模。我们提出一种增强采样策略，将势垒平坦化偏差与哈密顿量副本交换相结合，加速Mg²⁺内壳层结合达几个数量级，能定量探索大型核酶中的离子结合基序。该方法基于在CASP16 RNA溶剂化结构盲评中表现出色的方法。利用冷冻电镜图谱验证，引入局部分析框架从与实验密度的一致性推断单个结合基序的丰度。结果表明内壳层结合采样不足导致与实验一致性差，当前实验分辨率下预测不同内/外结合平衡的力场难以区分。这些结果凸显采样在二价离子结合建模中的主导作用，并提供了在复杂生物分子系统中将模拟与实验数据整合的通用策略。
英文摘要：
Magnesium ions are essential for RNA structure but difficult to model due to slow binding kinetics and experimental limitations. We present an enhanced-sampling strategy that accelerates Mg$^{2+}$ inner-shell binding by orders of magnitude, enabling quantitative exploration of ion-binding motifs in a large ribozyme. The method combines a barrier-flattening bias with Hamiltonian replica exchange to efficiently sample multiple equivalent binding sites, and builds on an approach that achieved top performance in the CASP16 blind assessment of RNA solvation structure. Using cryo-electron microscopy maps for validation, we introduce a local analysis framework that infers the population of individual binding motifs from their agreement with experimental density, enabling site-by-site validation. We find that insufficient sampling of inner-shell binding leads to significantly poorer agreement with experiment, whereas force fields predicting different inner/outer binding equilibria remain largely indistinguishable at the current experimental resolution. These results highlight the dominant role of sampling in modelling divalent ion binding and provide a general strategy for integrating simulations with experimental data in complex biomolecular systems.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
