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Integrating 3D structural information into systems biology

Systems biology is a data-heavy field that focuses on systems-wide depictions of biological phenomena necessarily sacrificing a detailed characterization of individual components. As an example, genome-wide protein interaction networks are widely used in systems biology and continuously extended and...

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Autores principales: Murray, Diana, Petrey, Donald, Honig, Barry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095114/
https://www.ncbi.nlm.nih.gov/pubmed/33744294
http://dx.doi.org/10.1016/j.jbc.2021.100562
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author Murray, Diana
Petrey, Donald
Honig, Barry
author_facet Murray, Diana
Petrey, Donald
Honig, Barry
author_sort Murray, Diana
collection PubMed
description Systems biology is a data-heavy field that focuses on systems-wide depictions of biological phenomena necessarily sacrificing a detailed characterization of individual components. As an example, genome-wide protein interaction networks are widely used in systems biology and continuously extended and refined as new sources of evidence become available. Despite the vast amount of information about individual protein structures and protein complexes that has accumulated in the past 50 years in the Protein Data Bank, the data, computational tools, and language of structural biology are not an integral part of systems biology. However, increasing effort has been devoted to this integration, and the related literature is reviewed here. Relationships between proteins that are detected via structural similarity offer a rich source of information not available from sequence similarity, and homology modeling can be used to leverage Protein Data Bank structures to produce 3D models for a significant fraction of many proteomes. A number of structure-informed genomic and cross-species (i.e., virus–host) interactomes will be described, and the unique information they provide will be illustrated with a number of examples. Tissue- and tumor-specific interactomes have also been developed through computational strategies that exploit patient information and through genetic interactions available from increasingly sensitive screens. Strategies to integrate structural information with these alternate data sources will be described. Finally, efforts to link protein structure space with chemical compound space offer novel sources of information in drug design, off-target identification, and the identification of targets for compounds found to be effective in phenotypic screens.
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spelling pubmed-80951142021-05-13 Integrating 3D structural information into systems biology Murray, Diana Petrey, Donald Honig, Barry J Biol Chem JBC Reviews Systems biology is a data-heavy field that focuses on systems-wide depictions of biological phenomena necessarily sacrificing a detailed characterization of individual components. As an example, genome-wide protein interaction networks are widely used in systems biology and continuously extended and refined as new sources of evidence become available. Despite the vast amount of information about individual protein structures and protein complexes that has accumulated in the past 50 years in the Protein Data Bank, the data, computational tools, and language of structural biology are not an integral part of systems biology. However, increasing effort has been devoted to this integration, and the related literature is reviewed here. Relationships between proteins that are detected via structural similarity offer a rich source of information not available from sequence similarity, and homology modeling can be used to leverage Protein Data Bank structures to produce 3D models for a significant fraction of many proteomes. A number of structure-informed genomic and cross-species (i.e., virus–host) interactomes will be described, and the unique information they provide will be illustrated with a number of examples. Tissue- and tumor-specific interactomes have also been developed through computational strategies that exploit patient information and through genetic interactions available from increasingly sensitive screens. Strategies to integrate structural information with these alternate data sources will be described. Finally, efforts to link protein structure space with chemical compound space offer novel sources of information in drug design, off-target identification, and the identification of targets for compounds found to be effective in phenotypic screens. American Society for Biochemistry and Molecular Biology 2021-03-18 /pmc/articles/PMC8095114/ /pubmed/33744294 http://dx.doi.org/10.1016/j.jbc.2021.100562 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle JBC Reviews
Murray, Diana
Petrey, Donald
Honig, Barry
Integrating 3D structural information into systems biology
title Integrating 3D structural information into systems biology
title_full Integrating 3D structural information into systems biology
title_fullStr Integrating 3D structural information into systems biology
title_full_unstemmed Integrating 3D structural information into systems biology
title_short Integrating 3D structural information into systems biology
title_sort integrating 3d structural information into systems biology
topic JBC Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095114/
https://www.ncbi.nlm.nih.gov/pubmed/33744294
http://dx.doi.org/10.1016/j.jbc.2021.100562
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