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Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds
The ability of target proteins to bind structurally diverse compounds and compounds with different degrees of promiscuity (multi-target activity) was systematically assessed on the basis of currently available activity data and target annotations. Intuitive first- and second-order target promiscuity...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441477/ https://www.ncbi.nlm.nih.gov/pubmed/26000736 http://dx.doi.org/10.1371/journal.pone.0126838 |
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author | Hu, Ye Bajorath, Jürgen |
author_facet | Hu, Ye Bajorath, Jürgen |
author_sort | Hu, Ye |
collection | PubMed |
description | The ability of target proteins to bind structurally diverse compounds and compounds with different degrees of promiscuity (multi-target activity) was systematically assessed on the basis of currently available activity data and target annotations. Intuitive first- and second-order target promiscuity indices were introduced to quantify these binding characteristics and relate them to each other. For compounds and targets, opposite promiscuity trends were observed. Furthermore, the analysis detected many targets that interacted with compounds representing a similar degree of structural diversity but displayed strong tendencies to recognize either promiscuous or selective compounds. Moreover, target families were identified that preferentially interacted with promiscuous compounds. Taken together, these findings further extend our understanding of the molecular basis of polypharmacology. |
format | Online Article Text |
id | pubmed-4441477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44414772015-05-28 Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds Hu, Ye Bajorath, Jürgen PLoS One Research Article The ability of target proteins to bind structurally diverse compounds and compounds with different degrees of promiscuity (multi-target activity) was systematically assessed on the basis of currently available activity data and target annotations. Intuitive first- and second-order target promiscuity indices were introduced to quantify these binding characteristics and relate them to each other. For compounds and targets, opposite promiscuity trends were observed. Furthermore, the analysis detected many targets that interacted with compounds representing a similar degree of structural diversity but displayed strong tendencies to recognize either promiscuous or selective compounds. Moreover, target families were identified that preferentially interacted with promiscuous compounds. Taken together, these findings further extend our understanding of the molecular basis of polypharmacology. Public Library of Science 2015-05-22 /pmc/articles/PMC4441477/ /pubmed/26000736 http://dx.doi.org/10.1371/journal.pone.0126838 Text en © 2015 Hu, Bajorath http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hu, Ye Bajorath, Jürgen Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds |
title | Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds |
title_full | Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds |
title_fullStr | Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds |
title_full_unstemmed | Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds |
title_short | Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds |
title_sort | quantifying the tendency of therapeutic target proteins to bind promiscuous or selective compounds |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441477/ https://www.ncbi.nlm.nih.gov/pubmed/26000736 http://dx.doi.org/10.1371/journal.pone.0126838 |
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