{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:04:29Z","timestamp":1789981469465,"version":"4.0.1"},"reference-count":77,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistryOpen"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    ERK2 plays a vital function in promoting cell survival and proliferation by phosphorylating various substrates. ERK2 is a key druggable target owing to its function in uncontrolled cell proliferation and cancer, making selective ERK2 inhibitors essential for treating aggressive malignancies. Peptides are promising therapeutic agents with strong biological activity, and frog skin\u2010derived peptides have shown notable anticancer potential. Seventeen curated frog skin\u2010derived anticancer peptides were modeled and docked against the ERK2 D\u2010recruitment site (DRS) using HADDOCK2.4 software. The predicted peptide\u2010DRS complexes were introduced to molecular dynamics simulations (MDS), and their binding energies (\u0394\n                    <jats:italic>G<\/jats:italic>\n                    <jats:sub>binding<\/jats:sub>\n                    ) were evaluated utilizing the MM\/GBSA approach. Upon MM\/GBSA\/\/200\u2009ns MDS, dermaseptin\u2010B3, dermaseptin\u2010PD\u20101, and ascaphin\u20108 showed better binding affinities against ERK2 DRS, with \u0394\n                    <jats:italic>G<\/jats:italic>\n                    <jats:sub>binding<\/jats:sub>\n                    values of \u221277.8, \u221274.1, and \u221256.7\u2009kcal\/mol, respectively, compared with the structurally resolved DRS\u2010binding reference peptide KIM\u2010MAP3 (\u0394\n                    <jats:italic>G<\/jats:italic>\n                    <jats:sub>binding<\/jats:sub>\n                    \u2009=\u2009\u221251.5\u2009kcal\/mol). Post\u2010MD analyses, including binding energy per trajectory and RMSD analyses, affirmed the great stability of the identified peptides complexed with ERK2 DRS over 200\u2009ns MDS. The predicted physicochemical features of the identified peptides indicated favorable functional potential. Collectively, these computational outcomes highlighted dermaseptin\u2010B3, dermaseptin\u2010PD\u20101, and ascaphin\u20108 as promising ERK2 DRS\u2010binding candidates. Further experimental validation is required to confirm their functional inhibitory activity.\n                  <\/jats:p>","DOI":"10.1002\/open.70295","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:44:37Z","timestamp":1787640277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the ERK2 Signaling Pathway With Frog Skin\u2010Derived Bioactive Peptides: Insights From Molecular Modeling, Molecular Dynamics, and Physicochemical Features"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3907-7091","authenticated-orcid":false,"given":"Nahlah Makki","family":"Almansour","sequence":"first","affiliation":[{"name":"Department of Biology College of Science University of Hafr Al Batin  Hafar Al Batin Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud M. H.","family":"Abdelhamid","sequence":"additional","affiliation":[{"name":"Computational Chemistry Laboratory Chemistry Department Faculty of Science Minia University  Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahraa","family":"Alali","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences College of Applied Medical Sciences University of Hafr Al Batin  Hafar Al Batin Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4819-2040","authenticated-orcid":false,"given":"Mahmoud A. A.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Computational Chemistry Laboratory Chemistry Department Faculty of Science Minia University  Minia Egypt"},{"name":"Department of Supportive Requirements University of Technology and Applied Sciences  Nizwa Sultanate of Oman"},{"name":"School of Health Sciences University of KwaZulu\u2010Natal  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(95)80063-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(97)80061-0"},{"key":"e_1_2_10_4_1","first-page":"49","volume-title":"Signal Transduction Through MAP Kinase Cascades","author":"Lewis T. 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