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A."},{"key":"10.1016\/j.ejphar.2026.179303_bib66","doi-asserted-by":"crossref","first-page":"14734","DOI":"10.1021\/bi026546a","article-title":"Two tarantula peptides inhibit activation of multiple sodium channels","volume":"41","author":"Middleton","year":"2002","journal-title":"Biochemistry"},{"key":"10.1016\/j.ejphar.2026.179303_bib67","doi-asserted-by":"crossref","first-page":"22707","DOI":"10.1074\/jbc.M113.461392","article-title":"Analysis of the structural and molecular basis of voltage-sensitive sodium channel inhibition by the spider toxin huwentoxin-IV (\u03bc-TRTX-Hh2a)","volume":"288","author":"Minassian","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2026.179303_bib68","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1021\/jm501765v","article-title":"Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel","volume":"58","author":"Murray","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejphar.2026.179303_bib69","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.str.2022.02.001","article-title":"Interface refinement of low- to medium-resolution Cryo-EM complexes using HADDOCK2.4","volume":"30","author":"Neijenhuis","year":"2022","journal-title":"Structure"},{"key":"10.1016\/j.ejphar.2026.179303_bib70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.1984.sp015320","article-title":"The surprising heart: a review of recent progress in cardiac electrophysiology","volume":"353","author":"Noble","year":"1984","journal-title":"J. Physiol."},{"key":"10.1016\/j.ejphar.2026.179303_bib71","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1006\/jmbi.2000.4042","article-title":"T-Coffee: a novel method for fast and accurate multiple sequence alignment","volume":"302","author":"Notredame","year":"2000","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ejphar.2026.179303_bib72","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.1749-6632.1986.tb15580.x","article-title":"Molecular structure of sodium channels","volume":"479","author":"Numa","year":"1986","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.ejphar.2026.179303_bib73","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/nature17976","article-title":"Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain","volume":"534","author":"Osteen","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2026.179303_bib74","doi-asserted-by":"crossref","first-page":"6836","DOI":"10.1073\/pnas.1621263114","article-title":"Pharmacology of the Na(v)1.1 domain IV voltage sensor reveals coupling between inactivation gating processes","volume":"114","author":"Osteen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejphar.2026.179303_bib75","doi-asserted-by":"crossref","DOI":"10.1126\/science.aau2486","article-title":"Structure of the human voltage-gated sodium channel Na(v)1.4 in complex with \u03b21","volume":"362","author":"Pan","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.ejphar.2026.179303_bib76","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.neulet.2010.06.050","article-title":"Electrophysiology and beyond: multiple roles of Na+ channel \u03b2 subunits in development and disease","volume":"486","author":"Patino","year":"2010","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.ejphar.2026.179303_bib77","doi-asserted-by":"crossref","DOI":"10.1063\/5.0014475","article-title":"Scalable molecular dynamics on CPU and GPU architectures with NAMD","volume":"153","author":"Phillips","year":"2020","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.ejphar.2026.179303_bib78","doi-asserted-by":"crossref","first-page":"L20","DOI":"10.1529\/biophysj.107.112375","article-title":"Is lipid bilayer binding a common property of inhibitor cysteine knot ion-channel blockers?","volume":"93","author":"Posokhov","year":"2007","journal-title":"Biophys. J."},{"key":"10.1016\/j.ejphar.2026.179303_bib79","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0173551","article-title":"The structure, dynamics and selectivity profile of a NaV1.7 potency-optimised huwentoxin-IV variant","volume":"12","author":"Rahnama","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2026.179303_bib80","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1093\/bioinformatics\/btq581","article-title":"Model quality assessment for membrane proteins","volume":"26","author":"Ray","year":"2010","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ejphar.2026.179303_bib81","first-page":"325","article-title":"Scorpion toxins: chemistry and mode of action","volume":"3","author":"Rochat","year":"1979","journal-title":"Adv. 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Biol. Chem."},{"key":"10.1016\/j.ejphar.2026.179303_bib86","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1124\/mol.107.041046","article-title":"Inhibition of sodium channel gating by trapping the domain II voltage sensor with protoxin II","volume":"73","author":"Sokolov","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.ejphar.2026.179303_bib87","doi-asserted-by":"crossref","first-page":"W246","DOI":"10.1093\/nar\/gku291","article-title":"AlignMe--a membrane protein sequence alignment web server","volume":"42","author":"Stamm","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejphar.2026.179303_bib88","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fphar.2011.00071","article-title":"Neurotoxins and their binding areas on voltage-gated sodium channels","volume":"2","author":"Stevens","year":"2011","journal-title":"Front. 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