Molecular dynamics simulations of an oligonucleotide duplex with adenine tracts phased by a full helix turn.
Molecular dynamics simulations of an oligonucleotide duplex with adenine tracts phased by a full helix turn.
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具有由全螺旋转角定相的腺嘌呤束的寡核苷酸双链体的分子动力学模拟。
DOI：
10.1006/jmbi.1998.1962
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Beveridge,DL
中科院分区：
文献类型：
--
作者：
Young,MA;Beveridge,DL
基于分子动力学计算机模拟，建立了一个以A区为特征的DNA寡核苷酸双链体的理论模型。在何种程度上，该模型同意与相关的实验数据轴弯曲和弯曲和螺旋形态的其他方面的关系的A-tracts。具体而言，一系列纳秒级的分子动力学（MD）模拟已经进行了25 bp的双链体d（ATAGGCAAAAAATAGGCAAAAATGG）在各种浓度的盐溶液。模拟由连接在一起的BamHI识别序列的三个10 bp重复组成的30个碱基对序列d（CGGGATCCCG·CGGGATCCCG·CGGGATCCCG）作为对照。MD使用AMBER 4.1程序套件进行，并利用Cornell等人的力场，静电边界条件由颗粒-网格Ewald求和协议处理。MD结果表明，在60 mM KCl，10 mM MgCl 2添加盐和最小中和阳离子的浓度下，MD模型显示出每个A道15.5°的一致轴弯曲。这与从环化实验推断的每转17至21°的弯曲相比是有利的。MD模型还显示出A束小沟区域从5′到3′逐渐变窄，这是从DNA足迹实验推断的特征。的MD模型的动态结构的分析表明，弯曲的起源如下的连接型弯曲模型与混合序列的效果的混合物，与A-tracts相对直，在寡核苷酸晶体结构的序列包含A-tracts。结果表明，是敏感的环境条件：MD对d（ATAGGCAAAAAATAGGCAAAAATGG）在中和Na+缓冲液的结果在显着减少曲率，和Mg 2+的去除可测量地影响弯曲。在实验盐条件下进行模拟似乎是必不可少的，以获得准确的帐户实验观察到的弯曲。
A theoretical model of a DNA oligonucleotide duplex featuring A-tracts phased by a full helix turn is developed based on molecular dynamics computer simulation. The extent to which this model agrees with relevant experimental data on axis bending and the relationship of A-tracts to bending and other aspects of helix morphology is investigated. Specifically, a series of nanosecond-level molecular dynamics (MD) simulations have been carried out for the 25 bp duplex d(ATAGGCAAAAAATAGGCAAAAATGG) at various concentrations of saline solution. A 30 base-pair sequence composed of three 10 bp repeats of the BamHI recognition sequence ligated together, d(CGGGATCCCG·CGGGATCCCG·CGGGATCCCG), was simulated as a control. The MD was carried out using the AMBER 4.1 suite of programs, and utilized the Cornell et al. force-field with the electrostatic boundary conditions treated by the particle-mesh Ewald summation protocol. The MD results show that at a concentration of 60 mM KCl, 10 mM MgCl2added salt plus minimal neutralizing cations, the MD model exhibits concerted axis bending to the extent of 15.5° per A-tract. This compares favorably with the bending per turn of 17 to 21° inferred from cyclization experiments. The MD model also exhibits a progressive 5′ to 3′ narrowing of the minor-groove region of A-tracts, a feature inferred from DNA footprinting experiments. Analysis of the dynamic structure of the MD models shows that the origin of the bending follows a junction-type bending model with an admixture of mixed sequence effects, with A-tracts relatively straight, as in oligonucleotide crystal structures of sequences containing A-tracts. The results are shown to be sensitive to environmental conditions: MD on d(ATAGGCAAAAAATAGGCAAAAATGG) in neutralizing Na+buffer results in markedly reduced curvature, and the removal of Mg2+measurably affects bending. Carrying out the simulations at experimental salt conditions appears to be essential to obtain an accurate account of the experimentally observed bending.