DNA的序列依赖性持久长度,Journal of Chemical Theory and Computation

当前位置： X-MOL 学术 › J. Chem. Theory Comput. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

DNA的序列依赖性持久长度
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2017-03-24 00:00:00 , DOI: 10.1021/acs.jctc.6b00904
Jonathan S. Mitchell ₁ , Jaroslaw Glowacki ₁ , Alexandre E. Grandchamp ₁ , Robert S. Manning ₂ , John H. Maddocks ₁

Affiliation

蒙特卡洛代码施加到cgDNA的粗粒硬质基模型B-形式的双链DNA用于预测序列平均持久的长度升_˚F在弗洛里的感= 53.5纳米，的升_p =在切线-切线相关性衰减的意义上为160 bp或53.5 nm。这些估计值略高于150 bp或50 nm的共识实验值，但鉴于cgDNA，我们认为协议是好的该模型本身是通过分子动力学模拟对长度为10–20 bp的短片段进行参数化的，与持久性长度没有明确的匹配。我们的蒙特卡洛模拟进一步预测，持久性长度可能与

片段的特定序列有很大的依赖关系。我们提出并确认了一个简单的因式分解的数值精度，该因式分解将

归因于固有形状的表观正切-正切相关性衰减的部分与

纯粹归因于刚度的部分（即所谓的依赖于序列的版本）分开序列平均动态持续长度ļ _d（= 58.8的内纳米cgDNA模型）。对于随机和λ噬菌体片段的集合，表观持久性长度的

序列标准偏差为4 nm，而我们的动态持久性长度

的标准偏差仅为1 nm。但是，存在显着的动态余辉长度离群值，包括poly（A）（异常平直和坚硬），poly（TA）（紧密盘绕且异常软）和A相序相序（异常弯曲和僵硬）。我们的数值模拟结果与分子动力学模拟和各种实验数据（包括微圆环化率和立体低温电子显微镜图像）都相当吻合。

"点击查看英文标题和摘要"

Sequence-Dependent Persistence Lengths of DNA

A Monte Carlo code applied to the cgDNA coarse-grain rigid-base model of B-form double-stranded DNA is used to predict a sequence-averaged persistence length of l_F = 53.5 nm in the sense of Flory, and of l_p = 160 bp or 53.5 nm in the sense of apparent tangent–tangent correlation decay. These estimates are slightly higher than the consensus experimental values of 150 bp or 50 nm, but we believe the agreement to be good given that the cgDNA model is itself parametrized from molecular dynamics simulations of short fragments of length 10–20 bp, with no explicit fit to persistence length. Our Monte Carlo simulations further predict that there can be substantial dependence of persistence lengths on the specific sequence

of a fragment. We propose, and confirm the numerical accuracy of, a simple factorization that separates the part of the apparent tangent–tangent correlation decay

attributable to intrinsic shape, from a part

attributable purely to stiffness, i.e., a sequence-dependent version of what has been called sequence-averaged dynamic persistence length l̅_d (=58.8 nm within the cgDNA model). For ensembles of both random and λ-phage fragments, the apparent persistence length

has a standard deviation of 4 nm over sequence, whereas our dynamic persistence length

has a standard deviation of only 1 nm. However, there are notable dynamic persistence length outliers, including poly(A) (exceptionally straight and stiff), poly(TA) (tightly coiled and exceptionally soft), and phased A-tract sequence motifs (exceptionally bent and stiff). The results of our numerical simulations agree reasonably well with both molecular dynamics simulation and diverse experimental data including minicircle cyclization rates and stereo cryo-electron microscopy images.

更新日期：2017-03-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南