{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:16:37Z","timestamp":1789038997473,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973227"],"award-info":[{"award-number":["81973227"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["LJKZ0936"],"award-info":[{"award-number":["LJKZ0936"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["LJKMZ20221359"],"award-info":[{"award-number":["LJKMZ20221359"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019-ZD-0462"],"award-info":[{"award-number":["2019-ZD-0462"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Basic Scientific Research Project of Colleges and University of Liaoning  Provincial Department of Education","award":["81973227"],"award-info":[{"award-number":["81973227"]}]},{"name":"Basic Scientific Research Project of Colleges and University of Liaoning  Provincial Department of Education","award":["LJKZ0936"],"award-info":[{"award-number":["LJKZ0936"]}]},{"name":"Basic Scientific Research Project of Colleges and University of Liaoning  Provincial Department of Education","award":["LJKMZ20221359"],"award-info":[{"award-number":["LJKMZ20221359"]}]},{"name":"Basic Scientific Research Project of Colleges and University of Liaoning  Provincial Department of Education","award":["2019-ZD-0462"],"award-info":[{"award-number":["2019-ZD-0462"]}]},{"name":"Liaoning Scientific Provincial Nature Fund Guidance Plan","award":["81973227"],"award-info":[{"award-number":["81973227"]}]},{"name":"Liaoning Scientific Provincial Nature Fund Guidance Plan","award":["LJKZ0936"],"award-info":[{"award-number":["LJKZ0936"]}]},{"name":"Liaoning Scientific Provincial Nature Fund Guidance Plan","award":["LJKMZ20221359"],"award-info":[{"award-number":["LJKMZ20221359"]}]},{"name":"Liaoning Scientific Provincial Nature Fund Guidance Plan","award":["2019-ZD-0462"],"award-info":[{"award-number":["2019-ZD-0462"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Voltage-gated sodium channels (VGSCs, or Nav) are important determinants of action potential generation and propagation. Efforts are underway to develop medicines targeting different channel subtypes for the treatment of related channelopathies. However, a high degree of conservation across its nine subtypes could lead to the off-target adverse effects on skeletal and cardiac muscles due to acting on primary skeletal muscle sodium channel Nav1.4 and cardiac muscle sodium channel Nav1.5, respectively. For a long evolutionary process, some peptide toxins from venoms have been found to be highly potent yet selective on ion channel subtypes and, therefore, hold the promising potential to be developed into therapeutic agents. In this research, all-atom molecular dynamic methods were used to elucidate the selective mechanisms of an analgesic-antitumor \u03b2-scorpion toxin (AGAP) with human Nav1.4 and Nav1.5 in order to unravel the primary reason for the production of its adverse reactions on the skeletal and cardiac muscles. Our results suggest that the rational distribution of residues with ring structures near position 38 and positive residues in the C-terminal on AGAP are critical factors to ensure its analgesic efficacy. Moreover, the substitution for residues with benzene is beneficial to reduce its side effects.<\/jats:p>","DOI":"10.3390\/toxins15010033","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T03:00:59Z","timestamp":1672628459000},"page":"33","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exploring the Pivotal Components Influencing the Side Effects Induced by an Analgesic-Antitumor Peptide from Scorpion Venom on Human Voltage-Gated Sodium Channels 1.4 and 1.5 through Computational Simulation"],"prefix":"10.3390","volume":"15","author":[{"given":"Fan","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangyi","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7268-0530","authenticated-orcid":false,"given":"Qi","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"He","sequence":"additional","affiliation":[{"name":"School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-4737","authenticated-orcid":false,"given":"Weizhuo","family":"Xu","sequence":"additional","affiliation":[{"name":"Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbo","family":"Song","sequence":"additional","affiliation":[{"name":"School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1152\/physrev.1992.72.suppl_4.S15","article-title":"Cellular and molecular biology of voltage-gated sodium channels","volume":"72","author":"Catterall","year":"1992","journal-title":"Physiol. 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