Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784673261621084160 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8942228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT oliveiraricardo modellingaptamerswithnucleicacidmimicsnamfromsequencetothreedimensionaldocking AT pinhoeva modellingaptamerswithnucleicacidmimicsnamfromsequencetothreedimensionaldocking AT sousaanaluisa modellingaptamerswithnucleicacidmimicsnamfromsequencetothreedimensionaldocking AT diasoscar modellingaptamerswithnucleicacidmimicsnamfromsequencetothreedimensionaldocking AT azevedonunofilipe modellingaptamerswithnucleicacidmimicsnamfromsequencetothreedimensionaldocking AT almeidacarina modellingaptamerswithnucleicacidmimicsnamfromsequencetothreedimensionaldocking |