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Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking

Aptamers are single-stranded oligonucleotides, formerly evolved by Systematic Evolution of Ligands by EXponential enrichment (SELEX), that fold into functional three-dimensional structures. Such conformation is crucial for aptamers’ ability to bind to a target with high affinity and specificity. Unn...

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Detalles Bibliográficos
Autores principales: Oliveira, Ricardo, Pinho, Eva, Sousa, Ana Luísa, Dias, Óscar, Azevedo, Nuno Filipe, Almeida, Carina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942228/
https://www.ncbi.nlm.nih.gov/pubmed/35320268
http://dx.doi.org/10.1371/journal.pone.0264701
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author Oliveira, Ricardo
Pinho, Eva
Sousa, Ana Luísa
Dias, Óscar
Azevedo, Nuno Filipe
Almeida, Carina
author_facet Oliveira, Ricardo
Pinho, Eva
Sousa, Ana Luísa
Dias, Óscar
Azevedo, Nuno Filipe
Almeida, Carina
author_sort Oliveira, Ricardo
collection PubMed
description Aptamers are single-stranded oligonucleotides, formerly evolved by Systematic Evolution of Ligands by EXponential enrichment (SELEX), that fold into functional three-dimensional structures. Such conformation is crucial for aptamers’ ability to bind to a target with high affinity and specificity. Unnatural nucleotides have been used to develop nucleic acid mimic (NAM) aptamers with increased performance, such as biological stability. Prior knowledge of aptamer-target interactions is critical for applying post-SELEX modifications with unnatural nucleotides since it can affect aptamers’ structure and performance. Here, we describe an easy-to-apply in silico workflow using free available software / web servers to predict the tertiary conformation of NAM, DNA and RNA aptamers, as well as the docking with the target molecule. Representative 2ʹ-O-methyl (2ʹOMe), locked nucleic acid (LNA), DNA and RNA aptamers, with experimental data deposited in Protein Data Bank, were selected to validate the workflow. All aptamers’ tertiary structure and docking models were successfully predicted with good structural similarity to the experimental data. Thus, this workflow will boost the development of aptamers, particularly NAM aptamers, by assisting in the rational modification of specific nucleotides and avoiding trial-and-error approaches.
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spelling pubmed-89422282022-03-24 Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking Oliveira, Ricardo Pinho, Eva Sousa, Ana Luísa Dias, Óscar Azevedo, Nuno Filipe Almeida, Carina PLoS One Research Article Aptamers are single-stranded oligonucleotides, formerly evolved by Systematic Evolution of Ligands by EXponential enrichment (SELEX), that fold into functional three-dimensional structures. Such conformation is crucial for aptamers’ ability to bind to a target with high affinity and specificity. Unnatural nucleotides have been used to develop nucleic acid mimic (NAM) aptamers with increased performance, such as biological stability. Prior knowledge of aptamer-target interactions is critical for applying post-SELEX modifications with unnatural nucleotides since it can affect aptamers’ structure and performance. Here, we describe an easy-to-apply in silico workflow using free available software / web servers to predict the tertiary conformation of NAM, DNA and RNA aptamers, as well as the docking with the target molecule. Representative 2ʹ-O-methyl (2ʹOMe), locked nucleic acid (LNA), DNA and RNA aptamers, with experimental data deposited in Protein Data Bank, were selected to validate the workflow. All aptamers’ tertiary structure and docking models were successfully predicted with good structural similarity to the experimental data. Thus, this workflow will boost the development of aptamers, particularly NAM aptamers, by assisting in the rational modification of specific nucleotides and avoiding trial-and-error approaches. Public Library of Science 2022-03-23 /pmc/articles/PMC8942228/ /pubmed/35320268 http://dx.doi.org/10.1371/journal.pone.0264701 Text en © 2022 Oliveira et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Oliveira, Ricardo
Pinho, Eva
Sousa, Ana Luísa
Dias, Óscar
Azevedo, Nuno Filipe
Almeida, Carina
Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking
title Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking
title_full Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking
title_fullStr Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking
title_full_unstemmed Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking
title_short Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking
title_sort modelling aptamers with nucleic acid mimics (nam): from sequence to three-dimensional docking
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942228/
https://www.ncbi.nlm.nih.gov/pubmed/35320268
http://dx.doi.org/10.1371/journal.pone.0264701
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