Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR model
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Journal of the Brazilian Chemical Society (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532012001100013 |
Resumo: | In this study, molecular docking and molecular dynamics (MD) simulations were conducted to investigate both the binding site and interactions of 61 inhibitors with activin-like kinase-5 (ALK5) receptor. A MD simulation was performed on the receptor to obtain receptor conformation in a water environment. Docking analysis revealed that hydrophobic and hydrogen bonding interactions play important roles in ALK5-inhibitor complex. These interactions were confirmed by X-ray crystallography. Furthermore, to study receptor conformation stability, a second MD simulation on complex was performed in an aqueous environment. Radius of gyration for complex showed that the ALK5 conformation did not change in the presence of the inhibitor. 134 descriptors emerging from docking and molecular structure were calculated and the most feasible ones were used in quantitative structure -activity relationships (QSAR). The LS-SVR (least squares support vector regression) gave reliable model with Q² = 0.837 and R = 0.917. Finally, the types of interactions and properties of the descriptors were used to propose new inhibitors. |
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Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR modelALK5dockingmolecular dynamics simulationleast squares support vector regressionQSARIn this study, molecular docking and molecular dynamics (MD) simulations were conducted to investigate both the binding site and interactions of 61 inhibitors with activin-like kinase-5 (ALK5) receptor. A MD simulation was performed on the receptor to obtain receptor conformation in a water environment. Docking analysis revealed that hydrophobic and hydrogen bonding interactions play important roles in ALK5-inhibitor complex. These interactions were confirmed by X-ray crystallography. Furthermore, to study receptor conformation stability, a second MD simulation on complex was performed in an aqueous environment. Radius of gyration for complex showed that the ALK5 conformation did not change in the presence of the inhibitor. 134 descriptors emerging from docking and molecular structure were calculated and the most feasible ones were used in quantitative structure -activity relationships (QSAR). The LS-SVR (least squares support vector regression) gave reliable model with Q² = 0.837 and R = 0.917. Finally, the types of interactions and properties of the descriptors were used to propose new inhibitors.Sociedade Brasileira de Química2012-11-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532012001100013Journal of the Brazilian Chemical Society v.23 n.11 2012reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.1590/S0103-50532012005000082info:eu-repo/semantics/openAccessEbrahimi,MaliheKhayamian,TaghiGharaghani,Sajjadeng2013-01-03T00:00:00Zoai:scielo:S0103-50532012001100013Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2013-01-03T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false |
dc.title.none.fl_str_mv |
Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR model |
title |
Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR model |
spellingShingle |
Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR model Ebrahimi,Malihe ALK5 docking molecular dynamics simulation least squares support vector regression QSAR |
title_short |
Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR model |
title_full |
Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR model |
title_fullStr |
Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR model |
title_full_unstemmed |
Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR model |
title_sort |
Interactions between Activin-Like Kinase 5 (ALK5) receptor and its inhibitors and the construction of a Docking Descriptor-Based QSAR model |
author |
Ebrahimi,Malihe |
author_facet |
Ebrahimi,Malihe Khayamian,Taghi Gharaghani,Sajjad |
author_role |
author |
author2 |
Khayamian,Taghi Gharaghani,Sajjad |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Ebrahimi,Malihe Khayamian,Taghi Gharaghani,Sajjad |
dc.subject.por.fl_str_mv |
ALK5 docking molecular dynamics simulation least squares support vector regression QSAR |
topic |
ALK5 docking molecular dynamics simulation least squares support vector regression QSAR |
description |
In this study, molecular docking and molecular dynamics (MD) simulations were conducted to investigate both the binding site and interactions of 61 inhibitors with activin-like kinase-5 (ALK5) receptor. A MD simulation was performed on the receptor to obtain receptor conformation in a water environment. Docking analysis revealed that hydrophobic and hydrogen bonding interactions play important roles in ALK5-inhibitor complex. These interactions were confirmed by X-ray crystallography. Furthermore, to study receptor conformation stability, a second MD simulation on complex was performed in an aqueous environment. Radius of gyration for complex showed that the ALK5 conformation did not change in the presence of the inhibitor. 134 descriptors emerging from docking and molecular structure were calculated and the most feasible ones were used in quantitative structure -activity relationships (QSAR). The LS-SVR (least squares support vector regression) gave reliable model with Q² = 0.837 and R = 0.917. Finally, the types of interactions and properties of the descriptors were used to propose new inhibitors. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-11-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532012001100013 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532012001100013 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S0103-50532012005000082 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
dc.source.none.fl_str_mv |
Journal of the Brazilian Chemical Society v.23 n.11 2012 reponame:Journal of the Brazilian Chemical Society (Online) instname:Sociedade Brasileira de Química (SBQ) instacron:SBQ |
instname_str |
Sociedade Brasileira de Química (SBQ) |
instacron_str |
SBQ |
institution |
SBQ |
reponame_str |
Journal of the Brazilian Chemical Society (Online) |
collection |
Journal of the Brazilian Chemical Society (Online) |
repository.name.fl_str_mv |
Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ) |
repository.mail.fl_str_mv |
||office@jbcs.sbq.org.br |
_version_ |
1750318174421647360 |