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Specificity quantification of biomolecular recognition and its implication for drug discovery
Highly efficient and specific biomolecular recognition requires both affinity and specificity. Previous quantitative descriptions of biomolecular recognition were mostly driven by improving the affinity prediction, but lack of quantification of specificity. We developed a novel method SPA (SPecifici...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298884/ https://www.ncbi.nlm.nih.gov/pubmed/22413060 http://dx.doi.org/10.1038/srep00309 |
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author | Yan, Zhiqiang Wang, Jin |
author_facet | Yan, Zhiqiang Wang, Jin |
author_sort | Yan, Zhiqiang |
collection | PubMed |
description | Highly efficient and specific biomolecular recognition requires both affinity and specificity. Previous quantitative descriptions of biomolecular recognition were mostly driven by improving the affinity prediction, but lack of quantification of specificity. We developed a novel method SPA (SPecificity and Affinity) based on our funneled energy landscape theory. The strategy is to simultaneously optimize the quantified specificity of the “native” protein-ligand complex discriminating against “non-native” binding modes and the affinity prediction. The benchmark testing of SPA shows the best performance against 16 other popular scoring functions in industry and academia on both prediction of binding affinity and “native” binding pose. For the target COX-2 of nonsteroidal anti-inflammatory drugs, SPA successfully discriminates the drugs from the diversity set, and the selective drugs from non-selective drugs. The remarkable performance demonstrates that SPA has significant potential applications in identifying lead compounds for drug discovery. |
format | Online Article Text |
id | pubmed-3298884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-32988842012-03-12 Specificity quantification of biomolecular recognition and its implication for drug discovery Yan, Zhiqiang Wang, Jin Sci Rep Article Highly efficient and specific biomolecular recognition requires both affinity and specificity. Previous quantitative descriptions of biomolecular recognition were mostly driven by improving the affinity prediction, but lack of quantification of specificity. We developed a novel method SPA (SPecificity and Affinity) based on our funneled energy landscape theory. The strategy is to simultaneously optimize the quantified specificity of the “native” protein-ligand complex discriminating against “non-native” binding modes and the affinity prediction. The benchmark testing of SPA shows the best performance against 16 other popular scoring functions in industry and academia on both prediction of binding affinity and “native” binding pose. For the target COX-2 of nonsteroidal anti-inflammatory drugs, SPA successfully discriminates the drugs from the diversity set, and the selective drugs from non-selective drugs. The remarkable performance demonstrates that SPA has significant potential applications in identifying lead compounds for drug discovery. Nature Publishing Group 2012-03-12 /pmc/articles/PMC3298884/ /pubmed/22413060 http://dx.doi.org/10.1038/srep00309 Text en Copyright © 2012, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareALike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Article Yan, Zhiqiang Wang, Jin Specificity quantification of biomolecular recognition and its implication for drug discovery |
title | Specificity quantification of biomolecular recognition and its implication for drug discovery |
title_full | Specificity quantification of biomolecular recognition and its implication for drug discovery |
title_fullStr | Specificity quantification of biomolecular recognition and its implication for drug discovery |
title_full_unstemmed | Specificity quantification of biomolecular recognition and its implication for drug discovery |
title_short | Specificity quantification of biomolecular recognition and its implication for drug discovery |
title_sort | specificity quantification of biomolecular recognition and its implication for drug discovery |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298884/ https://www.ncbi.nlm.nih.gov/pubmed/22413060 http://dx.doi.org/10.1038/srep00309 |
work_keys_str_mv | AT yanzhiqiang specificityquantificationofbiomolecularrecognitionanditsimplicationfordrugdiscovery AT wangjin specificityquantificationofbiomolecularrecognitionanditsimplicationfordrugdiscovery |