A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA.
A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA.
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DOI：
10.1093/nar/gkp834
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发表时间：
2010-01
影响因子：
14.9
通讯作者：
Sponer J
中科院分区：
文献类型：
--
作者：
Lavery R;Zakrzewska K;Beveridge D;Bishop TC;Case DA;Cheatham T 3rd;Dixit S;Jayaram B;Lankas F;Laughton C;Maddocks JH;Michon A;Osman R;Orozco M;Perez A;Singh T;Spackova N;Sponer J
众所周知，碱基序列对 DNA 的特性具有重大影响，并且在对细胞过程至关重要的蛋白质-DNA 相互作用中发挥着重要作用。理解和预测碱基序列效应需要广泛的结构和动态数据集，而目前实验无法提供这些数据集。因此成立了一个实验室联盟，以利用分子模拟来获取这些信息。本文描述的结果不仅提供有关所有 10 个独特碱基对步骤的信息，还提供有关这些步骤的所有可能的最近邻效应的信息。这些结果源自在显性溶剂中并使用生理盐浓度对 39 种不同 DNA 寡聚物进行 50-100 ns 的模拟。我们证明模拟在螺旋和主干参数方面是收敛的。结果表明，最近邻对碱基对步骤的影响非常显着，这意味着二核苷酸模型不足以预测序列依赖性行为。侧翼碱基序列尤其可以导致两个构象亚状态之间动态平衡的碱基对步进参数。尽管这项研究仅提供了关于次近邻效应的有限数据，但我们建议在尝试预测 DNA 序列依赖性行为之前应分析此类效应。
It is well recognized that base sequence exerts a significant influence on the properties of DNA and plays a significant role in protein–DNA interactions vital for cellular processes. Understanding and predicting base sequence effects requires an extensive structural and dynamic dataset which is currently unavailable from experiment. A consortium of laboratories was consequently formed to obtain this information using molecular simulations. This article describes results providing information not only on all 10 unique base pair steps, but also on all possible nearest-neighbor effects on these steps. These results are derived from simulations of 50–100 ns on 39 different DNA oligomers in explicit solvent and using a physiological salt concentration. We demonstrate that the simulations are converged in terms of helical and backbone parameters. The results show that nearest-neighbor effects on base pair steps are very significant, implying that dinucleotide models are insufficient for predicting sequence-dependent behavior. Flanking base sequences can notably lead to base pair step parameters in dynamic equilibrium between two conformational sub-states. Although this study only provides limited data on next-nearest-neighbor effects, we suggest that such effects should be analyzed before attempting to predict the sequence-dependent behavior of DNA.
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影响因子：
14.9
作者：
Giudice, E;Várnai, P;Lavery, R
通讯作者：
Lavery, R
影响因子：
14.9
作者：
DICKERSON, RE
通讯作者：
DICKERSON, RE
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG
影响因子：
5.8
作者：
Dixit, SB;Beveridge, DL
通讯作者：
Beveridge, DL
DOI：
10.1073/pnas.91.9.3579
发表时间：
1994-04-26
影响因子：
11.1
作者：
DICKERSON, RE;GOODSELL, DS;NEIDLE, S
通讯作者：
NEIDLE, S