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mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions
Over the past two decades, several computational methods have been proposed to predict how missense mutations can affect protein structure and function, either by altering protein stability or interactions with its partners, shedding light into potential molecular mechanisms giving rise to different...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570212/ https://www.ncbi.nlm.nih.gov/pubmed/28383703 http://dx.doi.org/10.1093/nar/gkx236 |
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author | Pires, Douglas E.V. Ascher, David B. |
author_facet | Pires, Douglas E.V. Ascher, David B. |
author_sort | Pires, Douglas E.V. |
collection | PubMed |
description | Over the past two decades, several computational methods have been proposed to predict how missense mutations can affect protein structure and function, either by altering protein stability or interactions with its partners, shedding light into potential molecular mechanisms giving rise to different phenotypes. Effectively and efficiently predicting consequences of mutations on protein–nucleic acid interactions, however, remained until recently a great and unmet challenge. Here we report an updated webserver for mCSM–NA, the only scalable method we are aware of capable of quantitatively predicting the effects of mutations in protein coding regions on nucleic acid binding affinities. We have significantly enhanced the original method by including a pharmacophore modelling and information of nucleic acid properties into our graph-based signatures, considering the reverse mutation and by using a refined, more reliable data set, based on a new release of the ProNIT database, which has significantly improved the reliability and applicability of the methodology. Our new predictive model was capable of achieving a correlation coefficient of up to 0.70 on cross-validation and 0.68 on blind-tests, outperforming its previous version. The server is freely available via a user-friendly web interface at: http://structure.bioc.cam.ac.uk/mcsm_na. |
format | Online Article Text |
id | pubmed-5570212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55702122017-08-29 mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions Pires, Douglas E.V. Ascher, David B. Nucleic Acids Res Web Server Issue Over the past two decades, several computational methods have been proposed to predict how missense mutations can affect protein structure and function, either by altering protein stability or interactions with its partners, shedding light into potential molecular mechanisms giving rise to different phenotypes. Effectively and efficiently predicting consequences of mutations on protein–nucleic acid interactions, however, remained until recently a great and unmet challenge. Here we report an updated webserver for mCSM–NA, the only scalable method we are aware of capable of quantitatively predicting the effects of mutations in protein coding regions on nucleic acid binding affinities. We have significantly enhanced the original method by including a pharmacophore modelling and information of nucleic acid properties into our graph-based signatures, considering the reverse mutation and by using a refined, more reliable data set, based on a new release of the ProNIT database, which has significantly improved the reliability and applicability of the methodology. Our new predictive model was capable of achieving a correlation coefficient of up to 0.70 on cross-validation and 0.68 on blind-tests, outperforming its previous version. The server is freely available via a user-friendly web interface at: http://structure.bioc.cam.ac.uk/mcsm_na. Oxford University Press 2017-07-03 2017-04-04 /pmc/articles/PMC5570212/ /pubmed/28383703 http://dx.doi.org/10.1093/nar/gkx236 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Web Server Issue Pires, Douglas E.V. Ascher, David B. mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions |
title | mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions |
title_full | mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions |
title_fullStr | mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions |
title_full_unstemmed | mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions |
title_short | mCSM–NA: predicting the effects of mutations on protein–nucleic acids interactions |
title_sort | mcsm–na: predicting the effects of mutations on protein–nucleic acids interactions |
topic | Web Server Issue |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570212/ https://www.ncbi.nlm.nih.gov/pubmed/28383703 http://dx.doi.org/10.1093/nar/gkx236 |
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