The use of molecular dynamics (MD) calculations to derive relative populations of conformers is highly sensitive to both timescale and parameterisation of the MD. Where these calculations are coupled with NOE data to determine the dynamics of a molecular system, this can present issues if these populations are thus relied upon. We present an approach that refines the highly accurate PANIC NMR methodology combined with clustering approaches to generate conformers, but without restraining the simulations or considering the relative population distributions generated by MD. Combining this structural sampling with NOE fitting, we demonstrate, for S-adenosylmethionine (aqueous solution at pH 7.0), significant improvements are made to the fit of populations to the experimental data, revealing a strong overall preference for the syn conformation of the adenosyl group relative to the ribose ring, but with less discrimination for the conformation of the ribose ring itself.

中文翻译：

---

基于分子力学数据改进柔性分子的 NOE 拟合——S-腺苷甲硫氨酸的案例研究†

使用分子动力学 (MD) 计算来推导构象异构体的相对群体对 MD 的时间尺度和参数化高度敏感。在这些计算与 NOE 数据相结合以确定分子系统的动力学的情况下，如果因此依赖这些种群，这可能会出现问题。我们提出了一种改进高精度 PANIC NMR 方法并结合聚类方法生成构象异构体的方法，但不限制模拟或考虑 MD 生成的相对人口分布。将这种结构采样与 NOE 拟合相结合，我们证明，对于S-腺苷甲硫氨酸（pH 7.0 的水溶液），显着改善了群体对实验数据的拟合，揭示了腺苷基团相对于核糖环的顺式构象的强烈总体偏好，但对构象的区分较少核糖环本身。