A single nucleotide resolution model for large-scale simulations of double stranded DNA

被引:20
作者
Fosado, Y. A. G. [1 ]
Michieletto, D. [1 ]
Allan, J. [2 ]
Brackley, C. A. [1 ]
Henrich, O. [1 ,3 ]
Marenduzzo, D. [1 ]
机构
[1] Univ Edinburgh, Sch Phys & Astron, Peter Guthrie Tait Rd, Edinburgh EH9 3FD, Midlothian, Scotland
[2] Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland
[3] Univ Edinburgh, EPCC, Peter Guthrie Tait Rd, Edinburgh EH9 3FD, Midlothian, Scotland
基金
英国工程与自然科学研究理事会; 欧洲研究理事会;
关键词
MOLECULAR-STRUCTURE; LINKING NUMBER; DENATURATION; ACID; ELASTICITY; DYNAMICS; FLEXIBILITY;
D O I
10.1039/c6sm01859a
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
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.
引用
收藏
页码:9458 / 9470
页数:13
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