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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0264701 |
| _version_ | 1818312726619881472 |
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| author | Ricardo Oliveira Eva Pinho Ana Luísa Sousa Óscar Dias Nuno Filipe Azevedo Carina Almeida |
| author_facet | Ricardo Oliveira Eva Pinho Ana Luísa Sousa Óscar Dias Nuno Filipe Azevedo Carina Almeida |
| author_sort | Ricardo Oliveira |
| collection | DOAJ |
| 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 2'-O-methyl (2'OMe), 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. |
| first_indexed | 2024-12-13T08:22:26Z |
| format | Article |
| id | doaj.art-3180d50c69334276bd2cf71f3d713439 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T08:22:26Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3180d50c69334276bd2cf71f3d7134392022-12-21T23:53:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01173e026470110.1371/journal.pone.0264701Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking.Ricardo OliveiraEva PinhoAna Luísa SousaÓscar DiasNuno Filipe AzevedoCarina AlmeidaAptamers 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 2'-O-methyl (2'OMe), 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.https://doi.org/10.1371/journal.pone.0264701 |
| spellingShingle | Ricardo Oliveira Eva Pinho Ana Luísa Sousa Óscar Dias Nuno Filipe Azevedo Carina Almeida Modelling aptamers with nucleic acid mimics (NAM): From sequence to three-dimensional docking. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0264701 |
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