Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.

Homology models of mammalian voltage-gated sodium (NaV) channels based on the crystal structures of the bacterial counterparts are needed to interpret the functional data on sodium channels and understand how they operate. Such models would also be invaluable in structure-based design of therapeutic...

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Autores principales:	Somayeh Mahdavi, Serdar Kuyucak
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7ecc3b3c585244768dcc3287faf5de43
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spelling	oai:doaj.org-article:7ecc3b3c585244768dcc3287faf5de432021-11-25T06:04:17ZMolecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.1932-620310.1371/journal.pone.0105300https://doaj.org/article/7ecc3b3c585244768dcc3287faf5de432014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25133704/?tool=EBIhttps://doaj.org/toc/1932-6203Homology models of mammalian voltage-gated sodium (NaV) channels based on the crystal structures of the bacterial counterparts are needed to interpret the functional data on sodium channels and understand how they operate. Such models would also be invaluable in structure-based design of therapeutics for diseases involving sodium channels such as chronic pain and heart diseases. Here we construct a homology model for the pore domain of the NaV1.4 channel and use the functional data for the binding of µ-conotoxin GIIIA to NaV1.4 to validate the model. The initial poses for the NaV1.4-GIIIA complex are obtained using the HADDOCK protein docking program, which are then refined in molecular dynamics simulations. The binding mode for the final complex is shown to be in broad agreement with the available mutagenesis data. The standard binding free energy, determined from the potential of mean force calculations, is also in good agreement with the experimental value. Because the pore domains of NaV1 channels are highly homologous, the model constructed for NaV1.4 will provide an excellent template for other NaV1 channels.Somayeh MahdaviSerdar KuyucakPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e105300 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Somayeh Mahdavi Serdar Kuyucak Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.
description	Homology models of mammalian voltage-gated sodium (NaV) channels based on the crystal structures of the bacterial counterparts are needed to interpret the functional data on sodium channels and understand how they operate. Such models would also be invaluable in structure-based design of therapeutics for diseases involving sodium channels such as chronic pain and heart diseases. Here we construct a homology model for the pore domain of the NaV1.4 channel and use the functional data for the binding of µ-conotoxin GIIIA to NaV1.4 to validate the model. The initial poses for the NaV1.4-GIIIA complex are obtained using the HADDOCK protein docking program, which are then refined in molecular dynamics simulations. The binding mode for the final complex is shown to be in broad agreement with the available mutagenesis data. The standard binding free energy, determined from the potential of mean force calculations, is also in good agreement with the experimental value. Because the pore domains of NaV1 channels are highly homologous, the model constructed for NaV1.4 will provide an excellent template for other NaV1 channels.
format	article
author	Somayeh Mahdavi Serdar Kuyucak
author_facet	Somayeh Mahdavi Serdar Kuyucak
author_sort	Somayeh Mahdavi
title	Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.
title_short	Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.
title_full	Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.
title_fullStr	Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.
title_full_unstemmed	Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.
title_sort	molecular dynamics study of binding of µ-conotoxin giiia to the voltage-gated sodium channel na(v)1.4.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7ecc3b3c585244768dcc3287faf5de43
work_keys_str_mv	AT somayehmahdavi moleculardynamicsstudyofbindingofμconotoxingiiiatothevoltagegatedsodiumchannelnav14 AT serdarkuyucak moleculardynamicsstudyofbindingofμconotoxingiiiatothevoltagegatedsodiumchannelnav14
_version_	1718414231352639488

Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4.

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