{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:07:11Z","timestamp":1790060831872,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Informatics"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    House fly (\n                    <jats:italic>Musca domestica<\/jats:italic>\n                    ) control faces mounting resistance to conventional insecticides, driving interest in novel chemistries targeting acetylcholinesterase (AChE). We examined eight benzenesulfonamide derivatives originally developed as carbonic anhydrase inhibitors to explore their potential as AChE\u2010targeting insecticides and to identify structural determinants of biological activity. Using a high\u2010quality homology model of\n                    <jats:italic>M. domestica<\/jats:italic>\n                    AChE, we performed blind docking, refined docking to the peripheral anionic site, 100\u2009ns molecular dynamics simulations, and molecular mechanics\u2010poisson\u2013boltzmann surface area (MM\u2010PBSA) binding energy calculations. All eight compounds showed favorable binding energies (\u22128.5 to \u221210.2\u2009kcal\/mol) and stable trajectories, yet bioassays revealed a stark divide: five compounds (16b, 16c, 16d, 19b, and 19f) produced no mortality at 5% concentration, while 14g and 17c achieved complete adult kill at 5% with LC\n                    <jats:sub>50<\/jats:sub>\n                    values of 1.37% (95% CI: 1.15%\u20131.63%) and 1.64% (95% CI: 1.38%\u20131.95%), respectively. The critical difference was geometric, not thermodynamic. Active compounds 14g and 17c penetrated the ~20\u2009\u00c5 aromatic gorge to position within 2.5\u20132.8\u2009\u00c5 of the catalytic serine (Ser318), forming hydrogen bonds and halogen bonds with the triad. Inactive compounds arrested at 7.0\u20137.5\u2009\u00c5, trapped in the peripheral anionic site with negligible catalytic residue contact despite favorable overall binding. This 4.5\u2009\u00c5 threshold correlated with biological activity and provided a quantitative filter for prioritizing AChE inhibitor candidates. Compound 14g, bearing 3,4\u2010dichloro substituents, showed the closest approach (2.5\u2009\u00c5) and strongest binding energy (\u221237.4 kcal\/mol), outperforming chlorpyrifos (\u221232.7 kcal\/mol). Importantly, whole\u2010organism mortality does not prove direct AChE inhibition; alternative mechanisms including cuticular penetration, metabolic disruption, or off\u2010target effects cannot be excluded without direct enzymatic assays. These findings suggest that geometric distance to the catalytic triad, not binding energy alone, correlates with biological activity and provides a quantitative filter for prioritizing AChE inhibitor candidates.\n                  <\/jats:p>","DOI":"10.1002\/minf.70054","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:04:58Z","timestamp":1789452298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural and Biological Evidence for Acetylcholinesterase\u2010Targeted Insecticidal Activity in\n                    <i>Musca domestica<\/i>\n                    : A 4.5\u2009 \u00c5 Distance Correlation From Novel Benzenesulfonamide Derivatives"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6407-0992","authenticated-orcid":false,"given":"Mohamed A.","family":"Bakry","sequence":"first","affiliation":[{"name":"Department of Parasitology Faculty of Veterinary Medicine Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa A.","family":"Kamel","sequence":"additional","affiliation":[{"name":"Department of Parasitology Faculty of Veterinary Medicine Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian N.","family":"Mahrous","sequence":"additional","affiliation":[{"name":"Department of Parasitology Faculty of Veterinary Medicine Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2165-9432","authenticated-orcid":false,"given":"Fatma I. Abo","family":"El\u2010Ela","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Veterinary Medicine Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael A. A.","family":"Fadaly","sequence":"additional","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1403-2527","authenticated-orcid":false,"given":"Shawky M.","family":"Aboelhadid","sequence":"additional","affiliation":[{"name":"Department of Parasitology Faculty of Veterinary Medicine Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574\u20106941.2011.01248.x"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/aesa\/saw083"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2300"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjtm.2018.09.007"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.4328"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1603\/0022\u20100493\u201093.4.1269"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3376\/1081\u20101710(2006)31[426:tsasco]2.0.co;2"},{"key":"e_1_2_12_9_1","unstructured":"D.Mota\u2010SanchezandJ. 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