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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...

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Detalles Bibliográficos
Autores principales: Yan, Zhiqiang, Wang, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
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.
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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
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