期刊
BIOPOLYMERS
卷 87, 期 1, 页码 40-50出版社
WILEY
DOI: 10.1002/bip.20769
关键词
nucleic acid; nitroxide; molecular dynamics (MD); distance measurement; conformation
资金
- NIGMS NIH HHS [R01 GM069557-01A3, R01 GM069557, R01 GM59297, R01 GM059297] Funding Source: Medline
Nanometer distances in nucleic acids can be measured by EPR using two 1-oxyl-2,2,5,5-tetraiiiethylpyrroline radicals, with each label attached via a methylene group to a phosphorothioate-substituted backbone position as one of two phosphorothloate diastereomers (R-p and S-p). Correlating the internitroxide distance to the geometry Of the parent molecule requires computational analysis of the label conformers. Here, we report sixteen 4-ns MD simulations on a DNA duplex d(CTACTGCTTTAG).d(CTAAAGCAGTAG) with label pairs at C71C19, T5/ A17, and T2/T14, respectively. For each labeled duplex, four simulations were performed with S-p/S-p,R-p/R-p S-p/ Rp and R-p/S-p labels, with initial all trans label conformations. Another set of four simulations was performed for the 7119-labeled duplex using a different label starting conformation. The average internitroxide distance (r(MD)) was within 0.2 A for the two sets of simulations for the 7119-labeled duplex, indicating sufficient sampling of conformational space. For all three labeled duplexes studied, (r(MD)) agreed with experimental values, as well as with average distances obtained from an efficient conformer search algorithm (NASNOX). The simulations also showed that the labels have conformational preferences determined by the linker chemistry and label-DNA interactions. These results establish computational algorithms that allow use of the 1-oxyl-2,2,5,5-tetramethylpyrroline label for mapping global structures of nucleic acids. (c) 2007 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据