Exploring the Mutational Robustness of Nucleic Acids by Searching Genotype Neighborhoods in Sequence Space

doi:10.1021/acs.jpclett.6b02769

	Exploring the Mutational Robustness of Nucleic Acids by Searching Genotype Neighborhoods in Sequence Space
	Zhou, Qingtong1 ; Sun, Xianbao 2; Xia, Xiaole 3; Fan, Zhou1,4,5,6 ; Luo, Zhaofeng 7; Zhao, Suwen1,6 ; Shakhnovich, Eugene 8; Liang, Haojun 2
	2017-01-19
发表期刊	JOURNAL OF PHYSICAL CHEMISTRY LETTERS (IF:4.8[JCR-2023],5.3[5-Year])
ISSN	1948-7185
卷号	8 期号:2 页码:407-414
发表状态	已发表
DOI	10.1021/acs.jpclett.6b02769
摘要	To assess the mutational robustness of nucleic acids, many genome- and protein-level studies have been performed, where nucleic acids are treated as genetic information carriers and transferrers. However, the molecular mechanisms through which mutations alter the structural, dynamic, and functional properties of nucleic acids are poorly understood. Here we performed a SELEX in silico study to investigate the fitness distribution of the L-Arm-binding aptamer genotype neighborhoods. Two novel functional genotype neighborhoods were isolated and experimentally verified to have comparable fitness as the wild-type. The experimental aptamer fitness landscape suggests the mutational robustness is strongly influenced by the local base environment and ligand-binding mode, whereas bases distant from the binding pocket provide potential evolutionary pathways to approach the global fitness maximum. Our work provides an example of successful application of SELEX in silico to optimize an aptamer and demonstrates the strong sensitivity of mutational robustness to the site of genetic variation.
收录类别	SCI ; EI
语种	英语
资助项目	National Institutes of Health[GM068670]
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS类目	Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Atomic, Molecular & Chemical
WOS记录号	WOS:000392560000015
出版者	AMER CHEMICAL SOC
EI入藏号	20171703590701
EI主题词	Binding energy ; Bins ; Genes ; Nucleic acids ; Sensitivity analysis
EI分类号	Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Storage:694.4 ; Biochemistry:801.2 ; Physical Chemistry:801.4 ; Mathematics:921
WOS关键词	MOLECULAR-DYNAMICS SIMULATIONS ; SINGLE-NUCLEOTIDE SUBSTITUTIONS ; IN-SILICO SELECTION ; DNA-APTAMER ; FITNESS LANDSCAPE ; EXPONENTIAL ENRICHMENT ; SYNTHETIC RIBOSWITCHES ; SYSTEMATIC EVOLUTION ; PROTEIN-BINDING ; VITRO SELECTION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1537
专题	生命科学与技术学院 iHuman研究所_特聘教授组_Andrej Sali组 iHuman研究所_PI研究组_赵素文组生命科学与技术学院_硕士生
通讯作者	Shakhnovich, Eugene; Liang, Haojun
作者单位	1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 2.Univ Sci & Technol China, Collaborat Innovat Ctr Chem Energy Mat, Hefei Natl Lab Phys Sci Microscale, CAS Key Lab Soft Matter Chem,Dept Polymer Sci & E, Hefei 230026, Anhui, Peoples R China 3.Jiangnan Univ, Sch Biotechnol, Key Lab Ind Biotechnol, Minist Educ, Wuxi 214122, Jiangsu, Peoples R China 4.Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Max Planck Independent Res Grp Populat Genom, Key Lab Computat Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 7.Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China 8.Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA
第一作者单位	iHuman研究所
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Zhou, Qingtong,Sun, Xianbao,Xia, Xiaole,et al. Exploring the Mutational Robustness of Nucleic Acids by Searching Genotype Neighborhoods in Sequence Space[J]. JOURNAL OF PHYSICAL CHEMISTRY LETTERS,2017,8(2):407-414.
APA	Zhou, Qingtong.,Sun, Xianbao.,Xia, Xiaole.,Fan, Zhou.,Luo, Zhaofeng.,...&Liang, Haojun.(2017).Exploring the Mutational Robustness of Nucleic Acids by Searching Genotype Neighborhoods in Sequence Space.JOURNAL OF PHYSICAL CHEMISTRY LETTERS,8(2),407-414.
MLA	Zhou, Qingtong,et al."Exploring the Mutational Robustness of Nucleic Acids by Searching Genotype Neighborhoods in Sequence Space".JOURNAL OF PHYSICAL CHEMISTRY LETTERS 8.2(2017):407-414.