DNA聚合酶复制速率对外力的依赖性：基于分子动力学模拟的模型
Dependence of DNA polymerase replication rate on external forces: a model based on molecular dynamics simulations.
作者信息
Andricioaei Ioan, Goel Anita, Herschbach Dudley, Karplus Martin
机构信息
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
出版信息
Biophys J. 2004 Sep;87(3):1478-97. doi: 10.1529/biophysj.103.039313.
Abstract
Molecular dynamics simulations are presented for a Thermus aquaticus (Taq) DNA polymerase I complex (consisting of the protein, the primer-template DNA strands, and the incoming nucleotide) subjected to external forces. The results obtained with a force applied to the DNA template strand provide insights into the effect of the tension on the activity of the enzyme. At forces below 30 pN a local model based on the parameters determined from the simulations, including the restricted motion of the DNA bases at the active site, yields a replication rate dependence on force in agreement with experiment. Simulations above 40 pN reveal large conformational changes in the enzyme-bound DNA that may have a role in the force-induced exonucleolysis observed experimentally.
摘要
本文展示了对嗜热水生栖热菌（Taq）DNA聚合酶I复合物（由蛋白质、引物-模板DNA链和进入的核苷酸组成）施加外力的分子动力学模拟。对DNA模板链施加力所获得的结果，为张力对酶活性的影响提供了见解。在低于30皮牛的力作用下，基于模拟确定的参数（包括活性位点处DNA碱基的受限运动）的局部模型，得出的复制速率与力的关系与实验相符。超过40皮牛的模拟显示，与酶结合的DNA发生了巨大的构象变化，这可能在实验观察到的力诱导的核酸外切作用中发挥作用。
相似文献
1
Dependence of DNA polymerase replication rate on external forces: a model based on molecular dynamics simulations.DNA聚合酶复制速率对外力的依赖性：基于分子动力学模拟的模型
Biophys J. 2004 Sep;87(3):1478-97. doi: 10.1529/biophysj.103.039313.
2
Mismatch-induced conformational distortions in polymerase beta support an induced-fit mechanism for fidelity.聚合酶β中错配诱导的构象畸变支持保真度的诱导契合机制。
Biochemistry. 2005 Oct 11;44(40):13328-41. doi: 10.1021/bi0507682.
3
Crystal structures of a ddATP-, ddTTP-, ddCTP, and ddGTP- trapped ternary complex of Klentaq1: insights into nucleotide incorporation and selectivity.Klentaq1的ddATP、ddTTP、ddCTP和ddGTP捕获三元复合物的晶体结构：对核苷酸掺入和选择性的见解。
Protein Sci. 2001 Jun;10(6):1225-33. doi: 10.1110/ps.250101.
4
Crystal structure of Thermus aquaticus DNA polymerase.嗜热水生栖热菌DNA聚合酶的晶体结构
Nature. 1995 Aug 17;376(6541):612-6. doi: 10.1038/376612a0.
5
Structural Insights into the Processing of Nucleobase-Modified Nucleotides by DNA Polymerases.DNA聚合酶对核碱基修饰核苷酸加工过程的结构见解
Acc Chem Res. 2016 Mar 15;49(3):418-27. doi: 10.1021/acs.accounts.5b00544. Epub 2016 Mar 5.
6
Computational study of the force dependence of phosphoryl transfer during DNA synthesis by a high fidelity polymerase.高保真聚合酶在DNA合成过程中磷酰基转移的力依赖性的计算研究。
Phys Rev Lett. 2008 Feb 29;100(8):088102. doi: 10.1103/PhysRevLett.100.088102. Epub 2008 Feb 26.
7
A three dimensional (3-D) physical model of DNA polymerase movement in DNA replication.
Biomed Sci Instrum. 2003;39:83-8.
8
Structure of Taq polymerase with DNA at the polymerase active site.在聚合酶活性位点处与DNA结合的Taq聚合酶的结构。
Nature. 1996 Jul 18;382(6588):278-81. doi: 10.1038/382278a0.
9
10
Evading the proofreading machinery of a replicative DNA polymerase: induction of a mutation by an environmental carcinogen.逃避复制性DNA聚合酶的校对机制：环境致癌物诱发的突变
J Mol Biol. 2001 Jun 1;309(2):519-36. doi: 10.1006/jmbi.2001.4674.
引用本文的文献
1
DNA replication: single-molecule manipulation data analysis and models.DNA复制：单分子操作数据分析与模型
Comput Struct Biotechnol J. 2021 Jun 24;19:3765-3778. doi: 10.1016/j.csbj.2021.06.032. eCollection 2021.
2
Replicative DNA polymerases promote active displacement of SSB proteins during lagging strand synthesis.复制 DNA 聚合酶在滞后链合成过程中促进 SSB 蛋白的主动置换。
Nucleic Acids Res. 2019 Jun 20;47(11):5723-5734. doi: 10.1093/nar/gkz249.
3
Single-molecule mechanochemical characterization of E. coli pol III core catalytic activity.大肠杆菌DNA聚合酶III核心催化活性的单分子机械化学特性研究
Protein Sci. 2017 Jul;26(7):1413-1426. doi: 10.1002/pro.3152. Epub 2017 Mar 16.
4
Free-energy landscape and characteristic forces for the initiation of DNA unzipping.DNA解链起始的自由能景观与特征力
Biophys J. 2015 Apr 7;108(7):1727-1738. doi: 10.1016/j.bpj.2015.01.025.
5
Dynamics of DNA polymerase I (Klenow fragment) under external force.DNA 聚合酶 I（Klenow 片段）在外力作用下的动力学。
J Mol Model. 2013 Mar;19(3):1379-89. doi: 10.1007/s00894-012-1688-5. Epub 2012 Nov 30.
6
Minimalist model for force-dependent DNA replication.力依赖性 DNA 复制的最简模型。
Biophys J. 2012 Feb 22;102(4):810-8. doi: 10.1016/j.bpj.2012.01.020. Epub 2012 Feb 21.
7
The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis.DNA 聚合酶 I 介导的 DNA 复制中转录步骤的机制：计算机模拟分析。
Structure. 2010 Jan 13;18(1):83-93. doi: 10.1016/j.str.2009.10.014.
8
Single-molecule study of DNA polymerization activity of HIV-1 reverse transcriptase on DNA templates.单分子研究 HIV-1 逆转录酶在 DNA 模板上的 DNA 聚合酶活性。
J Mol Biol. 2010 Feb 5;395(5):995-1006. doi: 10.1016/j.jmb.2009.11.072. Epub 2009 Dec 4.
9
Computational study of the force dependence of phosphoryl transfer during DNA synthesis by a high fidelity polymerase.高保真聚合酶在DNA合成过程中磷酰基转移的力依赖性的计算研究。
Phys Rev Lett. 2008 Feb 29;100(8):088102. doi: 10.1103/PhysRevLett.100.088102. Epub 2008 Feb 26.
10
Rotation of DNA around intact strand in human topoisomerase I implies distinct mechanisms for positive and negative supercoil relaxation.人类拓扑异构酶I中DNA围绕完整链的旋转意味着正负超螺旋松弛的不同机制。
Nucleic Acids Res. 2005 Nov 27;33(20):6621-34. doi: 10.1093/nar/gki935. Print 2005.
本文引用的文献
1
Interaction of DNA polymerase I (Klenow fragment) with the single-stranded template beyond the site of synthesis.DNA聚合酶I（克列诺片段）与合成位点以外的单链模板的相互作用。
Biochemistry. 2003 Mar 4;42(8):2373-85. doi: 10.1021/bi026566c.
2
Conformational dynamics of the chromatin fiber in solution: determinants, mechanisms, and functions.溶液中染色质纤维的构象动力学：决定因素、机制及功能
Annu Rev Biophys Biomol Struct. 2002;31:361-92. doi: 10.1146/annurev.biophys.31.101101.140858. Epub 2001 Oct 25.
3
Polymerase beta simulations suggest that Arg258 rotation is a slow step rather than large subdomain motions per se.聚合酶β模拟表明，精氨酸258的旋转是一个缓慢步骤，而非大的亚结构域运动本身。
J Mol Biol. 2002 Apr 12;317(5):651-71. doi: 10.1006/jmbi.2002.5450.
4
Unifying themes in DNA replication: reconciling single molecule kinetic studies with structural data on DNA polymerases.DNA复制中的统一主题：将单分子动力学研究与DNA聚合酶的结构数据相协调。
J Biomol Struct Dyn. 2002 Feb;19(4):571-84. doi: 10.1080/07391102.2002.10506764.
5
Uracil-DNA glycosylase acts by substrate autocatalysis.尿嘧啶-DNA糖基化酶通过底物自催化起作用。
Nature. 2001 Oct 18;413(6857):752-5. doi: 10.1038/35099587.
6
Getting a grip on how DNA polymerases function.掌握DNA聚合酶的作用机制。
Nat Struct Biol. 2001 Aug;8(8):656-9. doi: 10.1038/90344.
7
Tuning DNA "strings": modulating the rate of DNA replication with mechanical tension.调控DNA“弦线”：利用机械张力调节DNA复制速率
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8485-9. doi: 10.1073/pnas.151261198. Epub 2001 Jul 10.
8
Force and kinetic barriers to unzipping of the DNA double helix.DNA双螺旋解链的力和动力学障碍。
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8608-13. doi: 10.1073/pnas.151257598. Epub 2001 Jul 10.
9
Structure of the replicating complex of a pol alpha family DNA polymerase.一种α家族DNA聚合酶复制复合体的结构
Cell. 2001 Jun 1;105(5):657-67. doi: 10.1016/s0092-8674(01)00367-1.
10
Crystal structures of a ddATP-, ddTTP-, ddCTP, and ddGTP- trapped ternary complex of Klentaq1: insights into nucleotide incorporation and selectivity.Klentaq1的ddATP、ddTTP、ddCTP和ddGTP捕获三元复合物的晶体结构：对核苷酸掺入和选择性的见解。
Protein Sci. 2001 Jun;10(6):1225-33. doi: 10.1110/ps.250101.
Zotero 插件