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Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding
BACKGROUND: Protein-Protein Interactions (PPIs) are key for many cellular processes. The characterization of PPI interfaces and the prediction of putative ligand binding sites and hot spot residues are essential to design efficient small-molecule modulators of PPI. Terphenyl and its derivatives are...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689098/ https://www.ncbi.nlm.nih.gov/pubmed/23768251 http://dx.doi.org/10.1186/2050-6511-14-31 |
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author | Isvoran, Adriana Craciun, Dana Martiny, Virginie Sperandio, Olivier Miteva, Maria A |
author_facet | Isvoran, Adriana Craciun, Dana Martiny, Virginie Sperandio, Olivier Miteva, Maria A |
author_sort | Isvoran, Adriana |
collection | PubMed |
description | BACKGROUND: Protein-Protein Interactions (PPIs) are key for many cellular processes. The characterization of PPI interfaces and the prediction of putative ligand binding sites and hot spot residues are essential to design efficient small-molecule modulators of PPI. Terphenyl and its derivatives are small organic molecules known to mimic one face of protein-binding alpha-helical peptides. In this work we focus on several PPIs mediated by alpha-helical peptides. METHOD: We performed computational sequence- and structure-based analyses in order to evaluate several key physicochemical and surface properties of proteins known to interact with alpha-helical peptides and/or terphenyl and its derivatives. RESULTS: Sequence-based analysis revealed low sequence identity between some of the analyzed proteins binding alpha-helical peptides. Structure-based analysis was performed to calculate the volume, the fractal dimension roughness and the hydrophobicity of the binding regions. Besides the overall hydrophobic character of the binding pockets, some specificities were detected. We showed that the hydrophobicity is not uniformly distributed in different alpha-helix binding pockets that can help to identify key hydrophobic hot spots. CONCLUSIONS: The presence of hydrophobic cavities at the protein surface with a more complex shape than the entire protein surface seems to be an important property related to the ability of proteins to bind alpha-helical peptides and low molecular weight mimetics. Characterization of similarities and specificities of PPI binding sites can be helpful for further development of small molecules targeting alpha-helix binding proteins. |
format | Online Article Text |
id | pubmed-3689098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36890982013-06-27 Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding Isvoran, Adriana Craciun, Dana Martiny, Virginie Sperandio, Olivier Miteva, Maria A BMC Pharmacol Toxicol Research Article BACKGROUND: Protein-Protein Interactions (PPIs) are key for many cellular processes. The characterization of PPI interfaces and the prediction of putative ligand binding sites and hot spot residues are essential to design efficient small-molecule modulators of PPI. Terphenyl and its derivatives are small organic molecules known to mimic one face of protein-binding alpha-helical peptides. In this work we focus on several PPIs mediated by alpha-helical peptides. METHOD: We performed computational sequence- and structure-based analyses in order to evaluate several key physicochemical and surface properties of proteins known to interact with alpha-helical peptides and/or terphenyl and its derivatives. RESULTS: Sequence-based analysis revealed low sequence identity between some of the analyzed proteins binding alpha-helical peptides. Structure-based analysis was performed to calculate the volume, the fractal dimension roughness and the hydrophobicity of the binding regions. Besides the overall hydrophobic character of the binding pockets, some specificities were detected. We showed that the hydrophobicity is not uniformly distributed in different alpha-helix binding pockets that can help to identify key hydrophobic hot spots. CONCLUSIONS: The presence of hydrophobic cavities at the protein surface with a more complex shape than the entire protein surface seems to be an important property related to the ability of proteins to bind alpha-helical peptides and low molecular weight mimetics. Characterization of similarities and specificities of PPI binding sites can be helpful for further development of small molecules targeting alpha-helix binding proteins. BioMed Central 2013-06-14 /pmc/articles/PMC3689098/ /pubmed/23768251 http://dx.doi.org/10.1186/2050-6511-14-31 Text en Copyright © 2013 Isvoran et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Isvoran, Adriana Craciun, Dana Martiny, Virginie Sperandio, Olivier Miteva, Maria A Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding |
title | Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding |
title_full | Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding |
title_fullStr | Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding |
title_full_unstemmed | Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding |
title_short | Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding |
title_sort | computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689098/ https://www.ncbi.nlm.nih.gov/pubmed/23768251 http://dx.doi.org/10.1186/2050-6511-14-31 |
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