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Landscape of protein–small ligand binding modes
Elucidating the mechanisms of specific small‐molecule (ligand) recognition by proteins is a long‐standing conundrum. While the structures of these molecules, proteins and ligands, have been extensively studied, protein–ligand interactions, or binding modes, have not been comprehensively analyzed. Al...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338237/ https://www.ncbi.nlm.nih.gov/pubmed/27327045 http://dx.doi.org/10.1002/pro.2971 |
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author | Kasahara, Kota Kinoshita, Kengo |
author_facet | Kasahara, Kota Kinoshita, Kengo |
author_sort | Kasahara, Kota |
collection | PubMed |
description | Elucidating the mechanisms of specific small‐molecule (ligand) recognition by proteins is a long‐standing conundrum. While the structures of these molecules, proteins and ligands, have been extensively studied, protein–ligand interactions, or binding modes, have not been comprehensively analyzed. Although methods for assessing similarities of binding site structures have been extensively developed, the methods for the computational treatment of binding modes have not been well established. Here, we developed a computational method for encoding the information about binding modes as graphs, and assessing their similarities. An all‐against‐all comparison of 20,040 protein–ligand complexes provided the landscape of the protein–ligand binding modes and its relationships with protein‐ and chemical spaces. While similar proteins in the same SCOP Family tend to bind relatively similar ligands with similar binding modes, the correlation between ligand and binding similarities was not very high (R (2) = 0.443). We found many pairs with novel relationships, in which two evolutionally distant proteins recognize dissimilar ligands by similar binding modes (757,474 pairs out of 200,790,780 pairs were categorized into this relationship, in our dataset). In addition, there were an abundance of pairs of homologous proteins binding to similar ligands with different binding modes (68,217 pairs). Our results showed that many interesting relationships between protein–ligand complexes are still hidden in the structure database, and our new method for assessing binding mode similarities is effective to find them. |
format | Online Article Text |
id | pubmed-5338237 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53382372017-03-08 Landscape of protein–small ligand binding modes Kasahara, Kota Kinoshita, Kengo Protein Sci Articles Elucidating the mechanisms of specific small‐molecule (ligand) recognition by proteins is a long‐standing conundrum. While the structures of these molecules, proteins and ligands, have been extensively studied, protein–ligand interactions, or binding modes, have not been comprehensively analyzed. Although methods for assessing similarities of binding site structures have been extensively developed, the methods for the computational treatment of binding modes have not been well established. Here, we developed a computational method for encoding the information about binding modes as graphs, and assessing their similarities. An all‐against‐all comparison of 20,040 protein–ligand complexes provided the landscape of the protein–ligand binding modes and its relationships with protein‐ and chemical spaces. While similar proteins in the same SCOP Family tend to bind relatively similar ligands with similar binding modes, the correlation between ligand and binding similarities was not very high (R (2) = 0.443). We found many pairs with novel relationships, in which two evolutionally distant proteins recognize dissimilar ligands by similar binding modes (757,474 pairs out of 200,790,780 pairs were categorized into this relationship, in our dataset). In addition, there were an abundance of pairs of homologous proteins binding to similar ligands with different binding modes (68,217 pairs). Our results showed that many interesting relationships between protein–ligand complexes are still hidden in the structure database, and our new method for assessing binding mode similarities is effective to find them. John Wiley and Sons Inc. 2016-07-04 2016-09 /pmc/articles/PMC5338237/ /pubmed/27327045 http://dx.doi.org/10.1002/pro.2971 Text en © 2016 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Kasahara, Kota Kinoshita, Kengo Landscape of protein–small ligand binding modes |
title | Landscape of protein–small ligand binding modes |
title_full | Landscape of protein–small ligand binding modes |
title_fullStr | Landscape of protein–small ligand binding modes |
title_full_unstemmed | Landscape of protein–small ligand binding modes |
title_short | Landscape of protein–small ligand binding modes |
title_sort | landscape of protein–small ligand binding modes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338237/ https://www.ncbi.nlm.nih.gov/pubmed/27327045 http://dx.doi.org/10.1002/pro.2971 |
work_keys_str_mv | AT kasaharakota landscapeofproteinsmallligandbindingmodes AT kinoshitakengo landscapeofproteinsmallligandbindingmodes |