{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:16:54Z","timestamp":1788239814950,"version":"build-2803163510"},"reference-count":95,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM138217"],"award-info":[{"award-number":["R35GM138217"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["OIA\u20101757371"],"award-info":[{"award-number":["OIA\u20101757371"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Signaling through the insulin receptor (IR) and the type 1 insulin\u2010like growth factor receptor (IGF1R) is modulated by secreted hormones and growth factor ligands (e.g., insulin and insulin\u2010like growth factor 1, IGF1). Impaired signaling in these receptors often leads to diabetes and oncogenic diseases. The discovery of entirely novel viral insulin\/IGF\u2010like peptides (VILPs) that can stimulate receptors from the insulin family has raised questions about their structures and binding modes to receptors. These peptides exist in a single\u2010chain (sc) or a double\u2010chain (dc) configuration with folds likely similar to IGF1 and insulin, respectively. The interactions of VILPs with the human receptors are beginning to be mapped but little is known about their interactions with the receptors in fish\u2013the host organism for viruses known to carry these peptide sequences. We have previously reported [Chuard et\u00a0al. Cell Rep. 2025 44 (8):116149] structural models of several VILPs from the\n                    <jats:italic>Iridoviridae<\/jats:italic>\n                    virus family bound to their cognate receptors in Zebrafish (Zeb). In this work, we conducted all\u2010atom molecular dynamics (MD) simulations of these peptides and their receptor\u2010bound complexes along with free energy calculations to assess the energetic contributions of VILP residues for their binding to Zebrafish receptors. Most of the observed Zeb insulin\/Zeb\n                    <jats:italic>\u03bc<\/jats:italic>\n                    IR and Zeb IGF1\/Zeb\n                    <jats:italic>\u03bc<\/jats:italic>\n                    IGF1R site 1 interactions are consistent with previously known interactions of human peptides with their receptors, highlighting similarities in their binding modes. However, we also report some non\u2010conserved residues in VILPs that establish significant and unique interactions with residues in Zeb receptors. Furthermore, we identified residues in each VILP which can be potentially mutated into conserved insulin\/IGF1 residues to possibly enhance the binding affinity of these peptides.\n                  <\/jats:p>","DOI":"10.1002\/prot.70168","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:26:27Z","timestamp":1788236787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Interactions of Viral Insulin\/\n                    <scp>IGF<\/scp>\n                    \u2010Like Peptides With Zebrafish Receptors"],"prefix":"10.1002","author":[{"given":"Lev","family":"Levintov","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering and Bioengineering University of New Hampshire  Durham New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-2880","authenticated-orcid":false,"given":"Harish","family":"Vashisth","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Bioengineering University of New Hampshire  Durham New Hampshire USA"},{"name":"Department of Chemistry University of New Hampshire  Durham New Hampshire USA"},{"name":"Integrated Applied Mathematics Program University of New Hampshire  Durham New Hampshire USA"},{"name":"Molecular and Cellular Biotechnology Program University of New Hampshire  Durham New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"issue":"12","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1002\/bies.20151","article-title":"Insulin and Its Receptor: Structure, Function and Evolution","volume":"26","author":"De Meyts P.","year":"2004","journal-title":"BioEssays"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1007\/PL00000744","article-title":"Structure and Function of the Type 1 Insulin\u2010Like Growth Factor Receptor","volume":"57","author":"Adams T.","year":"2000","journal-title":"Cellular and Molecular Life Sciences"},{"issue":"4","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/bies.200800210","article-title":"Ligand\u2010Induced Activation of the Insulin Receptor: A Multi\u2010Step Process Involving Structural Changes in Both the Ligand and the Receptor","volume":"31","author":"Ward C. 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