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DBAC: A simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts
BACKGROUND: A protein binding hot spot is a cluster of residues in the interface that are energetically important for the binding of the protein with its interaction partner. Identifying protein binding hot spots can give useful information to protein engineering and drug design, and can also deepen...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121121/ https://www.ncbi.nlm.nih.gov/pubmed/21689480 http://dx.doi.org/10.1186/1752-0509-5-S1-S5 |
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author | Li, Zhenhua Wong, Limsoon Li, Jinyan |
author_facet | Li, Zhenhua Wong, Limsoon Li, Jinyan |
author_sort | Li, Zhenhua |
collection | PubMed |
description | BACKGROUND: A protein binding hot spot is a cluster of residues in the interface that are energetically important for the binding of the protein with its interaction partner. Identifying protein binding hot spots can give useful information to protein engineering and drug design, and can also deepen our understanding of protein-protein interaction. These residues are usually buried inside the interface with very low solvent accessible surface area (SASA). Thus SASA is widely used as an outstanding feature in hot spot prediction by many computational methods. However, SASA is not capable of distinguishing slightly buried residues, of which most are non hot spots, and deeply buried ones that are usually inside a hot spot. RESULTS: We propose a new descriptor called “burial level” for characterizing residues, atoms and atomic contacts. Specifically, burial level captures the depth the residues are buried. We identify different kinds of deeply buried atomic contacts (DBAC) at different burial levels that are directly broken in alanine substitution. We use their numbers as input for SVM to classify between hot spot or non hot spot residues. We achieve F measure of 0.6237 under the leave-one-out cross-validation on a data set containing 258 mutations. This performance is better than other computational methods. CONCLUSIONS: Our results show that hot spot residues tend to be deeply buried in the interface, not just having a low SASA value. This indicates that a high burial level is not only a necessary but also a more sufficient condition than a low SASA for a residue to be a hot spot residue. We find that those deeply buried atoms become increasingly more important when their burial levels rise up. This work also confirms the contribution of deeply buried interfacial atomic contacts to the energy of protein binding hot spot. |
format | Online Article Text |
id | pubmed-3121121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31211212011-06-23 DBAC: A simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts Li, Zhenhua Wong, Limsoon Li, Jinyan BMC Syst Biol Report BACKGROUND: A protein binding hot spot is a cluster of residues in the interface that are energetically important for the binding of the protein with its interaction partner. Identifying protein binding hot spots can give useful information to protein engineering and drug design, and can also deepen our understanding of protein-protein interaction. These residues are usually buried inside the interface with very low solvent accessible surface area (SASA). Thus SASA is widely used as an outstanding feature in hot spot prediction by many computational methods. However, SASA is not capable of distinguishing slightly buried residues, of which most are non hot spots, and deeply buried ones that are usually inside a hot spot. RESULTS: We propose a new descriptor called “burial level” for characterizing residues, atoms and atomic contacts. Specifically, burial level captures the depth the residues are buried. We identify different kinds of deeply buried atomic contacts (DBAC) at different burial levels that are directly broken in alanine substitution. We use their numbers as input for SVM to classify between hot spot or non hot spot residues. We achieve F measure of 0.6237 under the leave-one-out cross-validation on a data set containing 258 mutations. This performance is better than other computational methods. CONCLUSIONS: Our results show that hot spot residues tend to be deeply buried in the interface, not just having a low SASA value. This indicates that a high burial level is not only a necessary but also a more sufficient condition than a low SASA for a residue to be a hot spot residue. We find that those deeply buried atoms become increasingly more important when their burial levels rise up. This work also confirms the contribution of deeply buried interfacial atomic contacts to the energy of protein binding hot spot. BioMed Central 2011-06-20 /pmc/articles/PMC3121121/ /pubmed/21689480 http://dx.doi.org/10.1186/1752-0509-5-S1-S5 Text en Copyright ©2011 Li 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 | Report Li, Zhenhua Wong, Limsoon Li, Jinyan DBAC: A simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts |
title | DBAC: A simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts |
title_full | DBAC: A simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts |
title_fullStr | DBAC: A simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts |
title_full_unstemmed | DBAC: A simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts |
title_short | DBAC: A simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts |
title_sort | dbac: a simple prediction method for protein binding hot spots based on burial levels and deeply buried atomic contacts |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121121/ https://www.ncbi.nlm.nih.gov/pubmed/21689480 http://dx.doi.org/10.1186/1752-0509-5-S1-S5 |
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