A single nucleotide resolution model for large-scale simulations of double stranded DNA.
A single nucleotide resolution model for large-scale simulations of double stranded DNA.
复制标题
用于大规模模拟双链 DNA 的单核苷酸分辨率模型。
DOI：
10.1039/c6sm01859a
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发表时间：
2016
期刊：
影响因子：
3.4
通讯作者：
Fosado YA
中科院分区：
文献类型：
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作者：
Fosado YA
鉴于 DNA 纳米技术、单分子实验和体内 DNA 篡改的新进展，DNA 的计算建模变得至关重要。在这里，我们提出了单核苷酸水平双链 DNA (dsDNA) 的介观模型，该模型保留了特征性螺旋结构，同时能够模拟大分子（最多一百万个碱基对），以适应与生理过程相关的时间尺度。这是通过我们在此讨论的模型的高效且高度并行的实现来实现的。该模型捕捉了 DNA 的主要特征，例如双链和单链的不同持久长度、节距、扭转刚度以及主要和次要凹槽的存在。该模型构成了未来实现进一步功能的起点，例如序列特异性和静电排斥。我们表明，所提出的模型的行为与通过外力或扭矩操纵 dsDNA 的单分子实验相比较。我们最后提出了一些关于线性 DNA 变性和闭合双链 DNA 分子超螺旋动力学的结果。
The computational modelling of DNA is becoming crucial in light of new advances in DNA nano-technology, single-molecule experiments and in vivo DNA tampering. Here we present a mesoscopic model for double stranded DNA (dsDNA) at the single nucleotide level which retains the characteristic helical structure, while being able to simulate large molecules – up to a million base pairs – for time-scales which are relevant to physiological processes. This is made possible by an efficient and highly-parallelised implementation of the model which we discuss here. The model captures the main characteristics of DNA, such as the different persistence lengths for double and single strands, pitch, torsional rigidity and the presence of major and minor grooves. The model constitutes a starting point for the future implementation of further features, such as sequence specificity and electrostatic repulsion. We show that the behaviour of the presented model compares favourably with single molecule experiments where dsDNA is manipulated by external forces or torques. We finally present some results on the kinetics of denaturation of linear DNA and supercoiling of closed dsDNA molecules.