Understanding supercoiling-dependent DNA recognition: a combined experimental and computational approach

了解超螺旋依赖性 DNA 识别：实验和计算相结合的方法

• 批准号: BB/I019472/1
• 负责人: Sarah Harris
• 金额: $ 36.37万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI019472%2F1
• 关键词: Understanding; supercoiling; dependent; DNA; recognition

It is well known that DNA is the molecule of heredity and that the sequence of bases in DNA encodes the genetic information that defines an organism. DNA itself is generally organised in highly compacted structures, in particular supercoils in which the helical axis of DNA is coiled about itself. Supercoiling has a dramatic effect on the expression of genes and has been shown to act as a global regulator of gene expression. Our understanding of how supercoiling influences the behaviour of DNA is far from complete, particularly at the molecular level. Therefore we have developed a model system involving small DNA circles that we can analyse both by experimental methods and computer modelling. By combining these experimental and theoretical approaches we aim to understand how DNA recognition is affected by supercoiling, and how we can use supercoiling to influence biological processes.

众所周知，DNA是遗传的分子，DNA中的碱基序列编码了定义生物体的遗传信息。DNA本身通常以高度紧凑的结构组织，特别是超螺旋，其中DNA的螺旋轴围绕自身盘绕。超螺旋对基因的表达具有显著的影响，并且已被证明是基因表达的全局调节器。我们对超螺旋如何影响DNA行为的理解还远未完成，特别是在分子水平上。因此，我们开发了一个模型系统，涉及小的DNA环，我们可以通过实验方法和计算机建模进行分析。通过结合这些实验和理论方法，我们的目标是了解DNA识别如何受到超螺旋的影响，以及我们如何使用超螺旋来影响生物过程。

项目成果

Comparison of molecular contours for measuring writhe in atomistic supercoiled DNA.

• DOI: 10.1021/acs.jctc.5b00035
• 发表时间: 2015-06
• 期刊: Journal of chemical theory and computation
• 影响因子: 5.5
• 作者: T. Sutthibutpong;S. Harris;A. Noy

Protein/DNA interactions in complex DNA topologies: expect the unexpected.

• DOI: 10.1007/s12551-016-0208-8
• 发表时间: 2016
• 期刊: BIOPHYSICAL REVIEWS
• 作者: Noy, Agnes;Sutthibutpong, Thana;A Harris, Sarah
• 通讯作者: A Harris, Sarah

Small DNA circles as probes of DNA topology

• DOI: 10.1042/bst20120320
• 发表时间: 2013-04-01
• 期刊: BIOCHEMICAL SOCIETY TRANSACTIONS
• 影响因子: 3.9
• 作者: Bates, Andrew D.;Noy, Agnes;Maxwell, Anthony
• 通讯作者: Maxwell, Anthony

Seeing Supercoiled DNA with Atomistic Simulation: A New Twist on a Familiar Structure

通过原子模拟观察超螺旋 DNA：熟悉结构的新转折

• DOI: 10.1016/j.bpj.2017.11.111
• 发表时间: 2018
• 期刊: Biophysical Journal
• 影响因子: 3.4
• 作者: Harris S

Biomolecular simulations: From dynamics and mechanisms to computational assays of biological activity

• DOI: 10.1002/wcms.1393
• 发表时间: 2019-05-01
• 期刊: WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
• 影响因子: 11.4
• 作者: Huggins, David J.;Biggin, Philip C.;van der Kamp, Marc W.
• 通讯作者: van der Kamp, Marc W.