Symmetrization of the backbone of nucleic acids: a molecular dynamics study
Symmetrization of the backbone of nucleic acids: a molecular dynamics study
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核酸主链的对称化：分子动力学研究
DOI：
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发表时间：
2020
影响因子：
4.4
通讯作者：
B. Jayaram
中科院分区：
文献类型：
--
作者：
Pradeep Pant;A. Pathak;B. Jayaram
DNA显示方向不对称（5 ‘→3 ’），这是与每条核酸链相关的基本特性，对转录和复制等几个生物过程至关重要。我们观察到，这种不对称性可以通过多种方式改变，从而导致核酸方向对称。我们报告了六种创建对称骨架的方法，将其插入规则的B-DNA结构中，然后在显式溶剂中使用微秒时间尺度的分子动力学（MD）模拟对其进行表征。我们从螺旋形参数、二面体、凹槽几何形状和溶剂/离子可及性等方面比较了对称核酸与规则B-DNA的MD结构。我们还比较了这些对称分子与对照B-DNA系统的沃森-克里克氢键强度。通过结构和能能参数分析发现，设计少量取代基的对称dna保留了双螺旋B-DNA型结构。作为这种对称分子的应用，我们评估了带有短链互补RNA的单链对称核酸的结合自由能，发现设计的一些分子具有与对照DNA-RNA杂交系统相当的能量。由于寡核苷酸的化学修饰已成为控制核苷酸性质的重要工具，主要是核苷酸弯曲、与RNA靶标的结合以及对核酸酶的稳定性，从而设计核苷类药物类似物；所提出的对称分子在这些领域的重要性是可以预见的。由Ramaswamy H. Sarma传达
Abstract DNA displays directional asymmetry (5’→3’), a fundamental property associated with each strand of the nucleic acids and is crucial to several biological processes such as transcription and replication. We observe that this asymmetry can be altered by a number of ways leading to directionally symmetric nucleic acids. We report six such approaches for the creation of symmetric backbones, their insertion in a regular B-DNA structure followed by their characterization using molecular dynamics (MD) simulations on a microsecond timescale in explicit solvent. We compared the resultant MD structures of symmetric nucleic acids with that of regular B-DNA in terms of helicoidal parameters, dihedrals, groove geometry, and solvent/ions accessibility. We also compared the Watson-Crick hydrogen bond strength of these symmetric molecules to that of the control B-DNA system. It was found that the symmetric DNAs with a few substituents designed retained the double helical B-DNA type structure as seen by means of structural and energetic parameters. As an application of such symmetric molecules, we evaluated the binding free energies of single stranded symmetric nucleic acids with a short stretch of complementary RNA and found that a few molecules designed have comparable energies to that of control DNA-RNA hybrid system. As the chemical modifications in the oligonucleotides have been a remarkable tool for control over the nucleotide properties, mainly the nucleotide bending, binding to RNA targets, and stability to nucleases to design nucleoside drug analogs; the importance of the proposed symmetric molecules in these areas is foreseen. Communicated by Ramaswamy H. Sarma
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影响因子：
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