Toward Reproducing Sequence Trends in Phosphorus Chemical Shifts for Nucleic Acids by MD/DFT Calculations

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• 作者：Jana P艡ececht臎lov谩 ; Mark茅ta L. Munzarov谩 ; Juha Vaara ; Jan Novotn媒 ; Martin Dra膷铆nsk媒 ; Vladim铆r Sklen谩艡
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2013
• 出版时间：March 12, 2013
• 年：2013
• 卷：9
• 期：3
• 页码：1641-1656
• 全文大小：912K
• 年卷期：v.9,no.3(March 12, 2013)
• ISSN：1549-9626

文摘

This work addresses the question of the ability of the molecular dynamics鈥揹ensity functional theory (MD/DFT) approach to reproduce sequence trend in ³¹P chemical shifts (未P) in the backbone of nucleic acids. 未P for [d(CGCGAATTCGCG)]₂, a canonical B-DNA, have been computed using density functional theory calculations on model compounds with geometries cut out of snapshots of classical molecular dynamics (MD) simulations. The values of ³¹P chemical shifts for two distinct B-DNA subfamilies BI and BII, 未P/BI and 未P/BII, have been determined as averages over the BI and BII subparts of the MD trajectory. This has been done for various samplings of MD trajectory and for two sizes of both the model and the solvent embedding. For all of the combinations of trajectory sampling, model size, and embedding size, sequence dependence of 未P/BI in the order of 0.4鈥?.5 ppm has been obtained. Weighted averages for individual ³¹P nuclei in the studied DNA double-helix have been calculated from 未P/BI and 未P/BII using BI and BII percentages from free MD simulations as well as from approaches employing NMR structural restraints. A good qualitative agreement is found between experimental sequence trends in 未P and theoretical 未P employing short (24 ns) MD run and BI, BII percentages determined by Hartmann et al. or via MD with the inclusion of NMR structural restraints. Theoretical 未P exhibit a systematic offset of ca. 11 ppm and overestimation of trends by a factor of ca. 1.7. When scaled accordingly, theoretical 未P/BI and 未P/BII can be used to determine the expected percentage of BII to match the experimental value of 未P. As evidenced by the calculations on snapshots from Car鈥揚arrinello molecular dynamics, the systematic offsets of the theoretical 未P obtained by MD/DFT approach result primarily from the unrealistic bond lengths employed by classical MD. The findings made in this work provide structure鈭捨碢 relationships for possible use as NMR restraints and suggest that NMR calculations on MD snapshots can be in the future employed for the validation of newly developed force fields.