Rakesh Mukherjee, Aditya Sengar, Javier Cabello-García and Thomas E. Ouldridge*,
{"title":"动力学校对可增强非酶DNA链置换网络的特异性","authors":"Rakesh Mukherjee, Aditya Sengar, Javier Cabello-García and Thomas E. Ouldridge*, ","doi":"10.1021/jacs.3c14673","DOIUrl":null,"url":null,"abstract":"<p >Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimerization reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleotide mutations, both in terms of the initial rate with which the probe reacts and the long-time behavior.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacs.3c14673","citationCount":"0","resultStr":"{\"title\":\"Kinetic Proofreading Can Enhance Specificity in a Nonenzymatic DNA Strand Displacement Network\",\"authors\":\"Rakesh Mukherjee, Aditya Sengar, Javier Cabello-García and Thomas E. Ouldridge*, \",\"doi\":\"10.1021/jacs.3c14673\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimerization reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleotide mutations, both in terms of the initial rate with which the probe reacts and the long-time behavior.</p>\",\"PeriodicalId\":49,\"journal\":{\"name\":\"Journal of the American Chemical Society\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":14.4000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/epdf/10.1021/jacs.3c14673\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the American Chemical Society\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/jacs.3c14673\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/jacs.3c14673","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
整个自然系统都在使用动力校对来提高分子识别的特异性。在最基本的层面上,动能校对利用化学燃料的供应来驱动识别相互作用失去平衡,使正确目标和错误目标之间的单个自由能差被利用两次或更多次。尽管动能校对在生物学中非常重要,但在分子识别非常重要的合成系统中(如核酸纳米技术),却很少有人尝试采用动能校对。在本文中,我们介绍了一种基于 DNA 链位移的动力学校对模式,表明在模板化二聚反应过程中,DNA 燃料的消耗可用于增强分子识别。然后,我们展示了动力学校对可以从探针反应的初始速率和长期行为两方面提高探针辨别单核苷酸突变的特异性。
Kinetic Proofreading Can Enhance Specificity in a Nonenzymatic DNA Strand Displacement Network
Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimerization reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleotide mutations, both in terms of the initial rate with which the probe reacts and the long-time behavior.
期刊介绍:
The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.