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Extensive functional screening has identified a number of these peptides as modulators of the voltage\u2010gated sodium channel subtype Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7, a potential target for the treatment of chronic pain. In this study, we used a bioinformatic approach that can automatically identify Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 gating modifier toxins from sequence information alone. The method further enables the incorporation of evolutionarily accessible sequence space in structure\u2013activity relationship studies. The\n                    <jats:italic>in silico<\/jats:italic>\n                    method identified a putative Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibitor, \u03bc\u2010theraphotoxin Cg4a, which we produced recombinantly and confirmed as a Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibitor. Using structural and mutagenesis studies, we propose an improved definition of the pharmacophore of this class of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibitors, aiding future\n                    <jats:italic>in silico<\/jats:italic>\n                    screening and classification of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70036","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T04:55:26Z","timestamp":1744692926000},"page":"1717-1732","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Refining the\n                    <scp>\n                      Na\n                      <sub>V<\/sub>\n                      1\n                    <\/scp>\n                    .7 pharmacophore of a class of venom\u2010derived peptide inhibitors\n                    <i>via<\/i>\n                    a combination of\n                    <i>in\u00a0silico<\/i>\n                    screening and rational engineering"],"prefix":"10.1002","volume":"599","author":[{"given":"Gagan","family":"Sharma","sequence":"first","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology The University of Queensland  St Lucia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5107-8938","authenticated-orcid":false,"given":"Jennifer R.","family":"Deuis","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  St Lucia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinying","family":"Jia","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology The University of Queensland  St Lucia Australia"},{"name":"Department of Biochemistry National University of Singapore  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Crawford","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology The University of Queensland  St Lucia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sassan","family":"Rahnama","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology The University of Queensland  St Lucia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eivind A. 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