Modeling EphB4-EphrinB2 protein–protein interaction using flexible docking of a short linear motif
Abstract Background Many protein–protein interactions are mediated by a short linear motif. Usually, amino acid sequences of those motifs are known or can be predicted. It is much harder to experimentally characterize or predict their structure in the bound form. In this work, we test a possibility...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-08-01
|
| Series: | BioMedical Engineering OnLine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12938-017-0362-7 |
| _version_ | 1819130700900597760 |
|---|---|
| author | Maciej Pawel Ciemny Mateusz Kurcinski Maciej Blaszczyk Andrzej Kolinski Sebastian Kmiecik |
| author_facet | Maciej Pawel Ciemny Mateusz Kurcinski Maciej Blaszczyk Andrzej Kolinski Sebastian Kmiecik |
| author_sort | Maciej Pawel Ciemny |
| collection | DOAJ |
| description | Abstract Background Many protein–protein interactions are mediated by a short linear motif. Usually, amino acid sequences of those motifs are known or can be predicted. It is much harder to experimentally characterize or predict their structure in the bound form. In this work, we test a possibility of using flexible docking of a short linear motif to predict the interaction interface of the EphB4-EphrinB2 complex (a system extensively studied for its significance in tumor progression). Methods In the modeling, we only use knowledge about the motif sequence and experimental structures of EphB4-EphrinB2 complex partners. The proposed protocol enables efficient modeling of significant conformational changes in the short linear motif fragment during molecular docking simulation. For the docking simulations, we use the CABS-dock method for docking fully flexible peptides to flexible protein receptors (available as a server at http://biocomp.chem.uw.edu.pl/CABSdock/ ). Based on the docking result, the protein–protein complex is reconstructed and refined. Results Using this novel protocol, we obtained an accurate EphB4-EphrinB2 interaction model. Conclusions The results show that the CABS-dock method may be useful as the primary docking tool in specific protein–protein docking cases similar to EphB4-EphrinB2 complex—that is, where a short linear motif fragment can be identified. |
| first_indexed | 2024-12-22T09:03:47Z |
| format | Article |
| id | doaj.art-1d1b738cce874b63acd5db6269c79cbd |
| institution | Directory Open Access Journal |
| issn | 1475-925X |
| language | English |
| last_indexed | 2024-12-22T09:03:47Z |
| publishDate | 2017-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BioMedical Engineering OnLine |
| spelling | doaj.art-1d1b738cce874b63acd5db6269c79cbd2022-12-21T18:31:40ZengBMCBioMedical Engineering OnLine1475-925X2017-08-0116S11910.1186/s12938-017-0362-7Modeling EphB4-EphrinB2 protein–protein interaction using flexible docking of a short linear motifMaciej Pawel Ciemny0Mateusz Kurcinski1Maciej Blaszczyk2Andrzej Kolinski3Sebastian Kmiecik4Faculty of Chemistry, Biological and Chemical Research Centre, University of WarsawFaculty of Chemistry, Biological and Chemical Research Centre, University of WarsawFaculty of Chemistry, Biological and Chemical Research Centre, University of WarsawFaculty of Chemistry, Biological and Chemical Research Centre, University of WarsawFaculty of Chemistry, Biological and Chemical Research Centre, University of WarsawAbstract Background Many protein–protein interactions are mediated by a short linear motif. Usually, amino acid sequences of those motifs are known or can be predicted. It is much harder to experimentally characterize or predict their structure in the bound form. In this work, we test a possibility of using flexible docking of a short linear motif to predict the interaction interface of the EphB4-EphrinB2 complex (a system extensively studied for its significance in tumor progression). Methods In the modeling, we only use knowledge about the motif sequence and experimental structures of EphB4-EphrinB2 complex partners. The proposed protocol enables efficient modeling of significant conformational changes in the short linear motif fragment during molecular docking simulation. For the docking simulations, we use the CABS-dock method for docking fully flexible peptides to flexible protein receptors (available as a server at http://biocomp.chem.uw.edu.pl/CABSdock/ ). Based on the docking result, the protein–protein complex is reconstructed and refined. Results Using this novel protocol, we obtained an accurate EphB4-EphrinB2 interaction model. Conclusions The results show that the CABS-dock method may be useful as the primary docking tool in specific protein–protein docking cases similar to EphB4-EphrinB2 complex—that is, where a short linear motif fragment can be identified.http://link.springer.com/article/10.1186/s12938-017-0362-7Molecular dockingFlexible dockingProtein–peptide docking |
| spellingShingle | Maciej Pawel Ciemny Mateusz Kurcinski Maciej Blaszczyk Andrzej Kolinski Sebastian Kmiecik Modeling EphB4-EphrinB2 protein–protein interaction using flexible docking of a short linear motif BioMedical Engineering OnLine Molecular docking Flexible docking Protein–peptide docking |
| title | Modeling EphB4-EphrinB2 protein–protein interaction using flexible docking of a short linear motif |
| title_full | Modeling EphB4-EphrinB2 protein–protein interaction using flexible docking of a short linear motif |
| title_fullStr | Modeling EphB4-EphrinB2 protein–protein interaction using flexible docking of a short linear motif |
| title_full_unstemmed | Modeling EphB4-EphrinB2 protein–protein interaction using flexible docking of a short linear motif |
| title_short | Modeling EphB4-EphrinB2 protein–protein interaction using flexible docking of a short linear motif |
| title_sort | modeling ephb4 ephrinb2 protein protein interaction using flexible docking of a short linear motif |
| topic | Molecular docking Flexible docking Protein–peptide docking |
| url | http://link.springer.com/article/10.1186/s12938-017-0362-7 |
| work_keys_str_mv | AT maciejpawelciemny modelingephb4ephrinb2proteinproteininteractionusingflexibledockingofashortlinearmotif AT mateuszkurcinski modelingephb4ephrinb2proteinproteininteractionusingflexibledockingofashortlinearmotif AT maciejblaszczyk modelingephb4ephrinb2proteinproteininteractionusingflexibledockingofashortlinearmotif AT andrzejkolinski modelingephb4ephrinb2proteinproteininteractionusingflexibledockingofashortlinearmotif AT sebastiankmiecik modelingephb4ephrinb2proteinproteininteractionusingflexibledockingofashortlinearmotif |