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Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93
The transmembrane glycoprotein CD93 has been identified as a potential new target to inhibit tumor angiogenesis. Recently, Multimerin-2 (MMRN2), a pan-endothelial extracellular matrix protein, has been identified as a ligand for CD93, but the interaction mechanism between these two proteins is yet t...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638713/ https://www.ncbi.nlm.nih.gov/pubmed/36353214 http://dx.doi.org/10.3389/fbinf.2022.891553 |
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author | Cicaloni, Vittoria Karmakar, Malancha Frusciante, Luisa Pettini, Francesco Visibelli, Anna Orlandini, Maurizio Galvagni, Federico Mongiat, Maurizio Silk, Michael Nardi, Federica Ascher, David Santucci, Annalisa Spiga, Ottavia |
author_facet | Cicaloni, Vittoria Karmakar, Malancha Frusciante, Luisa Pettini, Francesco Visibelli, Anna Orlandini, Maurizio Galvagni, Federico Mongiat, Maurizio Silk, Michael Nardi, Federica Ascher, David Santucci, Annalisa Spiga, Ottavia |
author_sort | Cicaloni, Vittoria |
collection | PubMed |
description | The transmembrane glycoprotein CD93 has been identified as a potential new target to inhibit tumor angiogenesis. Recently, Multimerin-2 (MMRN2), a pan-endothelial extracellular matrix protein, has been identified as a ligand for CD93, but the interaction mechanism between these two proteins is yet to be studied. In this article, we aim to investigate the structural and functional effects of induced mutations on the binding domain of CD93 to MMRN2. Starting from experimental data, we assessed how specific mutations in the C-type lectin-like domain (CTLD) affect the binding interaction profile. We described a four-step workflow in order to predict the effects of variations on the inter-residue interaction network at the PPI, based on evolutionary information, complex network metrics, and energetic affinity. We showed that the application of computational approaches, combined with experimental data, allowed us to gain more in-depth molecular insights into the CD93–MMRN2 interaction, offering a platform for developing innovative therapeutics able to target these molecules and block their interaction. This comprehensive molecular insight might prove useful in drug design in cancer therapy. |
format | Online Article Text |
id | pubmed-9638713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96387132022-11-08 Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93 Cicaloni, Vittoria Karmakar, Malancha Frusciante, Luisa Pettini, Francesco Visibelli, Anna Orlandini, Maurizio Galvagni, Federico Mongiat, Maurizio Silk, Michael Nardi, Federica Ascher, David Santucci, Annalisa Spiga, Ottavia Front Bioinform Bioinformatics The transmembrane glycoprotein CD93 has been identified as a potential new target to inhibit tumor angiogenesis. Recently, Multimerin-2 (MMRN2), a pan-endothelial extracellular matrix protein, has been identified as a ligand for CD93, but the interaction mechanism between these two proteins is yet to be studied. In this article, we aim to investigate the structural and functional effects of induced mutations on the binding domain of CD93 to MMRN2. Starting from experimental data, we assessed how specific mutations in the C-type lectin-like domain (CTLD) affect the binding interaction profile. We described a four-step workflow in order to predict the effects of variations on the inter-residue interaction network at the PPI, based on evolutionary information, complex network metrics, and energetic affinity. We showed that the application of computational approaches, combined with experimental data, allowed us to gain more in-depth molecular insights into the CD93–MMRN2 interaction, offering a platform for developing innovative therapeutics able to target these molecules and block their interaction. This comprehensive molecular insight might prove useful in drug design in cancer therapy. Frontiers Media S.A. 2022-06-21 /pmc/articles/PMC9638713/ /pubmed/36353214 http://dx.doi.org/10.3389/fbinf.2022.891553 Text en Copyright © 2022 Cicaloni, Karmakar, Frusciante, Pettini, Visibelli, Orlandini, Galvagni, Mongiat, Silk, Nardi, Ascher, Santucci and Spiga. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioinformatics Cicaloni, Vittoria Karmakar, Malancha Frusciante, Luisa Pettini, Francesco Visibelli, Anna Orlandini, Maurizio Galvagni, Federico Mongiat, Maurizio Silk, Michael Nardi, Federica Ascher, David Santucci, Annalisa Spiga, Ottavia Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93 |
title | Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93 |
title_full | Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93 |
title_fullStr | Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93 |
title_full_unstemmed | Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93 |
title_short | Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93 |
title_sort | bioinformatics approaches to predict mutation effects in the binding site of the proangiogenic molecule cd93 |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638713/ https://www.ncbi.nlm.nih.gov/pubmed/36353214 http://dx.doi.org/10.3389/fbinf.2022.891553 |
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