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In Silico discovery of aptamers with an enhanced library design strategy
With advances in force fields and algorithms, robust tools have been developed for molecular simulation of three-dimensional structures of nucleic acids and investigation of aptamer-target interactions. The traditional aptamer discovery technique, Systematic Evolution of Ligands by EXponential enric...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Research Network of Computational and Structural Biotechnology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883144/ https://www.ncbi.nlm.nih.gov/pubmed/36733700 http://dx.doi.org/10.1016/j.csbj.2023.01.002 |
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author | Chen, Long Zhang, Bibi Wu, Zengrui Liu, Guixia Li, Weihua Tang, Yun |
author_facet | Chen, Long Zhang, Bibi Wu, Zengrui Liu, Guixia Li, Weihua Tang, Yun |
author_sort | Chen, Long |
collection | PubMed |
description | With advances in force fields and algorithms, robust tools have been developed for molecular simulation of three-dimensional structures of nucleic acids and investigation of aptamer-target interactions. The traditional aptamer discovery technique, Systematic Evolution of Ligands by EXponential enrichment (SELEX), continues to suffer from high investment and low return, while in vitro screening by simulated SELEX remains a challenging task, where more accurate structural modeling and enhanced sampling limit the large-scale application of the method. Here, we proposed a modified aptamer enhanced library design strategy to facilitate the screening of target-binding aptamers. In this strategy, a comprehensive analysis of the original complexes and the target secondary structure were used to construct an enhanced initial library for screening. Our enhanced sequence library design strategy based on the target secondary structure explored a certain sequence space while ensuring the accuracy of the structural conformation and the calculation method. In an enhanced library of only a few dozen sequences, four sequences showed a similar or better binding free energy than the original aptamer, with consistently high binding stability over three rounds of multi-timescale simulations, ranging from − 30.27 to − 32.25 kcal/mol. Consequently, the enhanced library strategy based on the target secondary structure is shown to have very significant potential as a new aptamer design and optimization strategy. |
format | Online Article Text |
id | pubmed-9883144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Research Network of Computational and Structural Biotechnology |
record_format | MEDLINE/PubMed |
spelling | pubmed-98831442023-02-01 In Silico discovery of aptamers with an enhanced library design strategy Chen, Long Zhang, Bibi Wu, Zengrui Liu, Guixia Li, Weihua Tang, Yun Comput Struct Biotechnol J Research Article With advances in force fields and algorithms, robust tools have been developed for molecular simulation of three-dimensional structures of nucleic acids and investigation of aptamer-target interactions. The traditional aptamer discovery technique, Systematic Evolution of Ligands by EXponential enrichment (SELEX), continues to suffer from high investment and low return, while in vitro screening by simulated SELEX remains a challenging task, where more accurate structural modeling and enhanced sampling limit the large-scale application of the method. Here, we proposed a modified aptamer enhanced library design strategy to facilitate the screening of target-binding aptamers. In this strategy, a comprehensive analysis of the original complexes and the target secondary structure were used to construct an enhanced initial library for screening. Our enhanced sequence library design strategy based on the target secondary structure explored a certain sequence space while ensuring the accuracy of the structural conformation and the calculation method. In an enhanced library of only a few dozen sequences, four sequences showed a similar or better binding free energy than the original aptamer, with consistently high binding stability over three rounds of multi-timescale simulations, ranging from − 30.27 to − 32.25 kcal/mol. Consequently, the enhanced library strategy based on the target secondary structure is shown to have very significant potential as a new aptamer design and optimization strategy. Research Network of Computational and Structural Biotechnology 2023-01-11 /pmc/articles/PMC9883144/ /pubmed/36733700 http://dx.doi.org/10.1016/j.csbj.2023.01.002 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Chen, Long Zhang, Bibi Wu, Zengrui Liu, Guixia Li, Weihua Tang, Yun In Silico discovery of aptamers with an enhanced library design strategy |
title | In Silico discovery of aptamers with an enhanced library design strategy |
title_full | In Silico discovery of aptamers with an enhanced library design strategy |
title_fullStr | In Silico discovery of aptamers with an enhanced library design strategy |
title_full_unstemmed | In Silico discovery of aptamers with an enhanced library design strategy |
title_short | In Silico discovery of aptamers with an enhanced library design strategy |
title_sort | in silico discovery of aptamers with an enhanced library design strategy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883144/ https://www.ncbi.nlm.nih.gov/pubmed/36733700 http://dx.doi.org/10.1016/j.csbj.2023.01.002 |
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