Stacking in RNA: NMR of Four Tetramers Benchmark Molecular Dynamics.
Stacking in RNA: NMR of Four Tetramers Benchmark Molecular Dynamics.
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DOI：
10.1021/ct501025q
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发表时间：
2015-06-09
影响因子：
5.5
通讯作者：
Turner, Douglas H.
中科院分区：
文献类型：
--
作者：
Condon, David E.;Kennedy, Scott D.;Mort, Brendan C.;Kierzek, Ryszard;Yildirim, Ilyas;Turner, Douglas H.
RNA四聚体r（AAAA）、r（CAAU）、r（GACC）和r（UUUU）的分子动力学（MD）模拟以1H-1H NOESY距离和3 J标量耦合为基准，以测试RNA扭转参数化的效果。四种不同的起始结构用于r（AAAA）、r（CAAU）和r（GACC），而五种起始结构用于r（UUUU）。在X射线结构的基础上，报告了用于量化堆叠的标准。力场AMBER ff 99、parmbsc 0、parm 99 x_Yil、ff 10和parmTor都预测了实验上未观察到的堆叠和嵌入，例如，碱基1堆叠在碱基3和碱基4之间，以及不正确的χ、χ 2和糖皱褶种群。嵌入结构特别稳定，通常持续几微秒。Parmbsc 0、parm 99 χ_Yil和ff 10给出与NMR类似的一致性，但最好的一致性仅为46%。实验上未观察到的插层通常与溶剂可及表面积的减少有关，沿着，氨基和羟基氢键与磷酸盐非桥氧键合。一组广泛的MD模拟结果表明，最近的力场参数化提高预测，但进一步的改进是必要的，以提供合理的协议与NMR。特别是，分子内堆积和氢键相互作用可能不会很好地平衡与TIP 3 P水模型。NMR数据和评分方法提供了严格的基准，为未来的变化力场和MD方法。
Molecular dynamics (MD) simulations for RNA tetramers r(AAAA), r(CAAU), r(GACC), and r(UUUU) are benchmarked against 1H–1H NOESY distances and 3J scalar couplings to test effects of RNA torsion parametrizations. Four different starting structures were used for r(AAAA), r(CAAU), and r(GACC), while five starting structures were used for r(UUUU). On the basis of X-ray structures, criteria are reported for quantifying stacking. The force fields, AMBER ff99, parmbsc0, parm99χ_Yil, ff10, and parmTor, all predict experimentally unobserved stacks and intercalations, e.g., base 1 stacked between bases 3 and 4, and incorrect χ, ϵ, and sugar pucker populations. The intercalated structures are particularly stable, often lasting several microseconds. Parmbsc0, parm99χ_Yil, and ff10 give similar agreement with NMR, but the best agreement is only 46%. Experimentally unobserved intercalations typically are associated with reduced solvent accessible surface area along with amino and hydroxyl hydrogen bonds to phosphate nonbridging oxygens. Results from an extensive set of MD simulations suggest that recent force field parametrizations improve predictions, but further improvements are necessary to provide reasonable agreement with NMR. In particular, intramolecular stacking and hydrogen bonding interactions may not be well balanced with the TIP3P water model. NMR data and the scoring method presented here provide rigorous benchmarks for future changes in force fields and MD methods.
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DOI：
10.1021/jp408909t
发表时间：
2014-02-06
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Condon DE;Yildirim I;Kennedy SD;Mort BC;Kierzek R;Turner DH
通讯作者：
Turner DH
影响因子：
5.5
作者：
Beauchamp, Kyle A.;Lin, Yu-Shan;Das, Rhiju;Pande, Vijay S.
通讯作者：
Pande, Vijay S.
DOI：
10.1073/pnas.1119057109
发表时间：
2012-01-17
影响因子：
11.1
作者：
Chen, Huimin;Meisburger, Steve P.;Pollack, Lois
通讯作者：
Pollack, Lois
影响因子：
15
作者：
ALTONA, C;SUNDARALINGAM, M
通讯作者：
SUNDARALINGAM, M
影响因子：
64.8
作者：
ARNOTT, S;HUKINS, DWL
通讯作者：
HUKINS, DWL