{"title":"Computational Identification and Illustrative Standard for Representation of Unimolecular G-Quadruplex Secondary Structures (CIIS-GQ)","authors":"Tugay Direk, Osman Doluca","doi":"10.1007/s10822-024-00573-1","DOIUrl":null,"url":null,"abstract":"<div><p>G-quadruplexes refer to a large group of nucleic acid–based structures. In recent years, they have been attracting attention due to their biological roles in the telomeres and promoter regions. These structures show wide diversity in topology, however, development of methods for structural classification of G-quadruplexes has been evaded for a long time. There has been a limited number of studies aiming to bring forth a secondary structure classification method. The situation was even more complex than imagined, since the discovery of bulged and mismatched G-quadruplexes while most of the available tools fail to distinguish these non-canonical G-quadruplex motifs. Moreover, the interpretation of their analysis output still requires expert knowledge. In this study, we propose a new method for identification of unimolecular G-Quadruplexes and classification by secondary structures based on three-dimensional structural data. Briefly, coordinates of guanines are processed to identify tetrads, loops and bulges. Then, we present the secondary structure in the form of a depiction which shows the loop types, bulges, and guanines that participate in each tetrad. Moreover, CIIS-GQ identifies non-guanine nucleotides that joins the G-tetrads and forms multiplets. Finally, the results of our study are compared with DSSR and ElTetrado classification methods, and the advantages of the proposed depiction method for representing secondary structures were discussed. The source code of the method can be accessed via https://github.com/TugayDirek/CIIS-GQ.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"38 1","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Computer-Aided Molecular Design","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10822-024-00573-1","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
G-quadruplexes refer to a large group of nucleic acid–based structures. In recent years, they have been attracting attention due to their biological roles in the telomeres and promoter regions. These structures show wide diversity in topology, however, development of methods for structural classification of G-quadruplexes has been evaded for a long time. There has been a limited number of studies aiming to bring forth a secondary structure classification method. The situation was even more complex than imagined, since the discovery of bulged and mismatched G-quadruplexes while most of the available tools fail to distinguish these non-canonical G-quadruplex motifs. Moreover, the interpretation of their analysis output still requires expert knowledge. In this study, we propose a new method for identification of unimolecular G-Quadruplexes and classification by secondary structures based on three-dimensional structural data. Briefly, coordinates of guanines are processed to identify tetrads, loops and bulges. Then, we present the secondary structure in the form of a depiction which shows the loop types, bulges, and guanines that participate in each tetrad. Moreover, CIIS-GQ identifies non-guanine nucleotides that joins the G-tetrads and forms multiplets. Finally, the results of our study are compared with DSSR and ElTetrado classification methods, and the advantages of the proposed depiction method for representing secondary structures were discussed. The source code of the method can be accessed via https://github.com/TugayDirek/CIIS-GQ.
G 型四聚体是指一大类基于核酸的结构。近年来,由于它们在端粒和启动子区域的生物学作用,它们一直备受关注。这些结构在拓扑结构上表现出广泛的多样性,然而,G-四重链结构分类方法的开发却迟迟没有进展。旨在提出二级结构分类方法的研究数量有限。情况比想象的还要复杂,因为人们发现了隆起和不匹配的 G 型四重结构,而大多数现有工具都无法区分这些非经典的 G 型四重结构图案。此外,对其分析结果的解释仍然需要专业知识。在这项研究中,我们提出了一种基于三维结构数据的新方法,用于识别单分子 G 型四核苷酸并根据二级结构进行分类。简而言之,通过处理鸟嘌呤的坐标来识别四聚体、环和凸起。然后,我们以描述的形式呈现二级结构,显示环路类型、隆起和参与每个四元组的鸟嘌呤。此外,CIIS-GQ 还能识别连接 G 四元组并形成多聚体的非鸟嘌呤核苷酸。最后,我们将研究结果与 DSSR 和 ElTetrado 分类方法进行了比较,并讨论了所提出的描述二级结构方法的优势。该方法的源代码可通过 https://github.com/TugayDirek/CIIS-GQ 访问。
期刊介绍:
The Journal of Computer-Aided Molecular Design provides a form for disseminating information on both the theory and the application of computer-based methods in the analysis and design of molecules. The scope of the journal encompasses papers which report new and original research and applications in the following areas:
- theoretical chemistry;
- computational chemistry;
- computer and molecular graphics;
- molecular modeling;
- protein engineering;
- drug design;
- expert systems;
- general structure-property relationships;
- molecular dynamics;
- chemical database development and usage.