骨架电负性对短链尺度DNA刚性的影响
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- 英文论文题名：The effects of backbone electrostatic repulsion on DNA rigidity on short length scales
- 论文作者：肖石燕 ; 陈李萍 ; 梁好均
- 英文论文作者：Shiyan Xiao ; Liping Chen ; Haojun Liang ; Key Laboratory of Soft Matter Chemistry ; Department of Polymer Science and Engineering ; University of Science and Technology of China ; Hefei National Laboratory for Physical Sciences at Microscale ; University of Science and Technology of China
- 年：2016
- 作者机构：中科院软物质化学重点实验室中国科学技术大学高分子科学与工程系;合肥微尺度物质科学国家实验室;
- 论文关键词：DNA ; 短链尺度 ; 刚性 ; 骨架中性化
- 会议召开时间：2016-08-25
- 会议录名称：中国化学会2016年软物质理论计算与模拟会议论文摘要集
- 语种：中文
- 分类号：Q523
- 学会代码：ZGHY
- 会议名称：中国化学会2016年软物质理论计算与模拟会议
- 会议地点：中国天津
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：2
- 文件大小：185k
- 原文格式：D
- 会议级别：全国
摘要
DNA是遗传物质的载体,是生物体中最重要的大分子之一。DNA骨架的磷酸基团带有很强的电负性,同时,分子内部通过互补配对形成的碱基对之间具有很强的π-π堆叠作用。这两种作用使DNA表现出很强的刚性[1]。通常,人们将DNA视为半刚性链,采用蠕虫链模型来描述DNA,其持久长度为50 nm,相当于150个碱基对(bp)的长度;对小于150 bp的DNA链段,则被视为刚性棒。但是,从生物功能的角度来看,短链尺度上DNA的结构和力学性质对DNA与蛋白质的相互作用,对其生理功能的完成具有十分重要的意义[2]。近年来,DNA在短链尺度上的结构和力学性质受到了人们的广泛关注。Wiggins[3]和Ha[4]等人的研究表明,DNA在小于100 bp的尺度上能够表现出很强的弯曲和形变,表明DNA在短链尺度上的表现偏离蠕虫链模型的假设。同时,对静电排斥作用和碱基对π-π堆叠作用,哪种效应对DNA的刚性贡献最大存在很大的争议[5-11]。为此,我们希望能够从DNA分子结构上去理解DNA在短链尺度上表现出来的柔顺性。基于对这个问题的思考,我们采用全原子分子动力学(atomic classical molecular dynamics,MD)模拟方法研究了DNA骨架电负性对DNA短链尺度刚性的影响。我们采用了Manning提出的"null isomer"模型[10],人为构建了一种DNA的异构体,从而将骨架电负性的贡献从DNA的总体刚性贡献中分离。通过比较正常和"中性化"DNA的性质,探讨DNA骨架电负性对短链尺度DNA结构和力学性质的影响。我们发现骨架静电排斥作用对DNA持久长度贡献符合manning的理论假设[10]。
Because of its critical role in the processes of cell cycle,the structural and physicochemical properties of DNA have long been of concern.The strong electrostatic repulsive interactions between the negatively charged phosphoryl groups of the nucleic acid backbone combined with the π-π stacking between neighboring base pairs(bp) make DNA a highly ordered and rigid molecule [1].Traditionally,DNA with its length longer than 1000 bp is treated as a semi-flexible chain,and can be described using the worm-like chain model,with the calculated value of its persistence length of 150 nm(~150 bp).The DNA fragment at sub-persistence scale is usually considered as a rigid "rod".From the viewpoint of molecule functions,the structural and mechanical properties of DNA less than 100 bp are essentially important in the interactions between DNA and protein,and in its biological activities in cellular environments.The recent studies of Wiggins [3] and Ha [4] demonstrated that DNA exhibits extreme bendability and structural flexibility,and these behaviors cannot be described using the traditional worm-like chain model.Moreover,there has still been no consensus for which effect until recently,the electrostatic repulsion from the backbone phosphate or the base pair stacking compression,contributes most to the DNA rigidity [5-11].In the present work,we tried to understand the extreme bendability of DNA less than 100 bp from the structural properties.To address this equations,atomic classical molecular dynamics was employed to study the effect of electrostatic repulsion from the backbone phosphates on the rigidity of DNA on short length scales.A neutralized DNA was built based on "null isomer" model suggested by Manning [10],which helps to extract the phosphate electrostatic repulsion from the overall effects resulting the DNA rigidity.Based on that,the effects of negative charges on the backbone phosphate on the DNA rigidity can be achieved through comparing the structure and dynamic conformational behaviors of a duplex in a normal form and its "null isomer" using molecular dynamics methods.Our results indicated that the electrostatic repulsion contributed ~10% to the persistence length of normal DNA,which is in accordance with the theory of Manning [10].
Because of its critical role in the processes of cell cycle,the structural and physicochemical properties of DNA have long been of concern.The strong electrostatic repulsive interactions between the negatively charged phosphoryl groups of the nucleic acid backbone combined with the π-π stacking between neighboring base pairs(bp) make DNA a highly ordered and rigid molecule [1].Traditionally,DNA with its length longer than 1000 bp is treated as a semi-flexible chain,and can be described using the worm-like chain model,with the calculated value of its persistence length of 150 nm(~150 bp).The DNA fragment at sub-persistence scale is usually considered as a rigid "rod".From the viewpoint of molecule functions,the structural and mechanical properties of DNA less than 100 bp are essentially important in the interactions between DNA and protein,and in its biological activities in cellular environments.The recent studies of Wiggins [3] and Ha [4] demonstrated that DNA exhibits extreme bendability and structural flexibility,and these behaviors cannot be described using the traditional worm-like chain model.Moreover,there has still been no consensus for which effect until recently,the electrostatic repulsion from the backbone phosphate or the base pair stacking compression,contributes most to the DNA rigidity [5-11].In the present work,we tried to understand the extreme bendability of DNA less than 100 bp from the structural properties.To address this equations,atomic classical molecular dynamics was employed to study the effect of electrostatic repulsion from the backbone phosphates on the rigidity of DNA on short length scales.A neutralized DNA was built based on "null isomer" model suggested by Manning [10],which helps to extract the phosphate electrostatic repulsion from the overall effects resulting the DNA rigidity.Based on that,the effects of negative charges on the backbone phosphate on the DNA rigidity can be achieved through comparing the structure and dynamic conformational behaviors of a duplex in a normal form and its "null isomer" using molecular dynamics methods.Our results indicated that the electrostatic repulsion contributed ~10% to the persistence length of normal DNA,which is in accordance with the theory of Manning [10].
引文
[1]S.Neidle,Principle of nucleic acid structure,Elsevier,New York,2008.
[2]B.Alberts,A.Johnson,J.Lewis,M.Raff,K.Roberts and P.Walter,Molecular Biology of The Cell,Garland Science,New York,London,5th edn,2007.
[3]Wiggins,P.A.;van der Heijden,T.;Moreno-Herrero,F.;Spakowitz,A.;Phillips,R.;Widom,J.;Dekker,C.;Nelson,P.C.Nature Nanotechnol.2006,1:137.
[4]Vafabakhsh,R.;Ha,T.Science 2012,337:1097.
[5]Bloomfield,V.A.Biopolymers 1997,44:269.
[6]Savelyev,A.;Materese,C.K.;Papoian,G.A.J.Am.Chem.Soc.2011,133:19290.
[7]Odijk,T.J.Polym.Sci.,Polym.Phys.Ed.1977,15:477.
[8]Skolnick,J.;Fixman,M.Macromolecules 1977,10:944.
[9]Baumann,C.G.;Smith,S.B.;Bloomfield,V.A.;Bustamante,C.Proc.Natl.Acad.Sci.U.S.A.1997,94:6185.
[10]Manning,G.S.Biophys.J.2006,91:3607.
[11]Podestá,A.;Indrieri,M.;Brogioli,D.;Manning,G.S.;Milani,P.;Guerra,R.;Finzi,L.;Dunlap,D.Biophys.J.2005,89:2558.
[2]B.Alberts,A.Johnson,J.Lewis,M.Raff,K.Roberts and P.Walter,Molecular Biology of The Cell,Garland Science,New York,London,5th edn,2007.
[3]Wiggins,P.A.;van der Heijden,T.;Moreno-Herrero,F.;Spakowitz,A.;Phillips,R.;Widom,J.;Dekker,C.;Nelson,P.C.Nature Nanotechnol.2006,1:137.
[4]Vafabakhsh,R.;Ha,T.Science 2012,337:1097.
[5]Bloomfield,V.A.Biopolymers 1997,44:269.
[6]Savelyev,A.;Materese,C.K.;Papoian,G.A.J.Am.Chem.Soc.2011,133:19290.
[7]Odijk,T.J.Polym.Sci.,Polym.Phys.Ed.1977,15:477.
[8]Skolnick,J.;Fixman,M.Macromolecules 1977,10:944.
[9]Baumann,C.G.;Smith,S.B.;Bloomfield,V.A.;Bustamante,C.Proc.Natl.Acad.Sci.U.S.A.1997,94:6185.
[10]Manning,G.S.Biophys.J.2006,91:3607.
[11]Podestá,A.;Indrieri,M.;Brogioli,D.;Manning,G.S.;Milani,P.;Guerra,R.;Finzi,L.;Dunlap,D.Biophys.J.2005,89:2558.