{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T01:24:57Z","timestamp":1780968297801,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bromo\u2010DragonFLY (BDF), a potent designer psychedelic drug with hallucinogenic properties, has recently emerged as a significant recreational substance. Named for its dragonfly\u2010like molecular structure, BDF induces prolonged psychedelic effects, with hallucinations lasting several days. Clinical reports highlight severe toxicity, including confusion, tachycardia, hypertension, seizures, renal failure, and, in extreme cases, death. BDF acts as a potent agonist of the 5\u2010HT2A serotonin receptor subtype, which mediates the behavioral and psychedelic effects of hallucinogens. Despite its increasing prevalence and associated clinical implications, the precise molecular mechanisms underlying BDF's interaction with 5\u2010HT2A remain inadequately characterized, particularly from an in silico perspective. This study addresses this gap by employing a comprehensive in silico framework to investigate the molecular interactions of BDF with the 5\u2010HT\n                    <jats:sub>2A<\/jats:sub>\n                    receptor. Molecular docking was used to identify binding sites, while all\u2010atom molecular dynamics (MD) simulations provided insights into the stability of the protein\u2010ligand complex, assessing deviations, local flexibility, and time\u2010dependent gyration patterns. The results revealed stable and compact complex formation between BDF and 5\u2010HT\n                    <jats:sub>2A<\/jats:sub>\n                    , characterized by minimal per\u2010residue fluctuations and high hydrogen bond occupancy, suggesting a highly stable interaction as shown experimentally. Additionally, principal component analysis, leveraging machine learning algorithms, demonstrated consistent motion, while free energy profiles highlighted stable energy basins with minimal variations for the BDF\u20105\u2010HT\n                    <jats:sub>2A<\/jats:sub>\n                    complex. These findings suggest strong binding affinities of BDF with the serotonin receptor, leading to highly stable complex formation. This study provides a foundational understanding of BDF's molecular interactions, offering critical insights into its role as a potent psychedelic agent and laying the groundwork for future investigations into the risks posed by novel designer drugs.\n                  <\/jats:p>","DOI":"10.1002\/prot.70055","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T09:27:26Z","timestamp":1758101246000},"page":"609-619","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Silico Characterization of Bromo\u2010\n                    <scp>DragonFLY<\/scp>\n                    Binding to the 5\u2010\n                    <scp>\n                      HT\n                      <sub>2A<\/sub>\n                    <\/scp>\n                    Receptor: Molecular Insights Into a Potent Designer Psychedelic"],"prefix":"10.1002","volume":"94","author":[{"given":"Syeda Sumayya","family":"Tariq","sequence":"first","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological Sciences, University of Karachi  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urooj","family":"Qureshi","sequence":"additional","affiliation":[{"name":"H.E.J. Research Institute of Chemistry International Center for Chemical and Biological Sciences, University of Karachi  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamona","family":"Mushtaq","sequence":"additional","affiliation":[{"name":"H.E.J. Research Institute of Chemistry International Center for Chemical and Biological Sciences, University of Karachi  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajida","family":"Munsif","sequence":"additional","affiliation":[{"name":"National &amp; Local United Engineering Laboratory for Power Batteries, Faculty of Chemistry Northeast Normal University  Changchun People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Nur\u2010e\u2010Alam","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy King Saud University  Riyadh Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed F.","family":"Hawwal","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy King Saud University  Riyadh Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences Guangxi Normal University  Guilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8530-8711","authenticated-orcid":false,"given":"Zaheer","family":"Ul\u2010Haq","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological Sciences, University of Karachi  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","first-page":"206","article-title":"Designer Drugs: An Escalating Public Health Challenge","volume":"6","author":"Madras B. K.","year":"2012","journal-title":"Journal of Global Drug Policy and Practice"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm000491y"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2008.11.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03178273"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2018.07.018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.4c00105"},{"issue":"16","key":"e_1_2_9_8_1","first-page":"1199","article-title":"Bromo\u2010Dragon Fly\u2010Life\u2010Threatening Drug. Can Cause Tissue Necrosis as Demonstrated by the First Described Case","volume":"105","author":"Thorlacius K.","year":"2008","journal-title":"L\u00e4kartidningen"},{"issue":"2","key":"e_1_2_9_9_1","first-page":"7","article-title":"Bromo\u2010DragonFLY\u2010Induced Dystonia","volume":"8","author":"Pletsch G.","year":"2013","journal-title":"Am J Psychiatry Res J"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00414-018-1882-9"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm9803525"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.711255"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.3c00267"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00225"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.5c02044"},{"key":"e_1_2_9_16_1","article-title":"Molecular Insights Into the Binding of Organophosphate Flame Retardant Key Metabolites With Mineralocorticoid and Estrogen Receptors","author":"Tariq S.","year":"2025","journal-title":"ACS Omega"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.comptc.2023.114211"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<490::AID-JCC1>3.0.CO;2-P"},{"key":"e_1_2_9_19_1","unstructured":"Chemical Computing Group \u201cMolecular Operating Environment (MOE) 2019.01 \u201d2020 Chemical Computing Group ULC 1010 Sherbooke St. West Suite #910; Montreal QC Canada."},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl8615"},{"key":"e_1_2_9_21_1","unstructured":"P.Labute \u201cProtonate 3D: Assignment of Macromolecular Protonation State and Geometry \u201d2007 Chemical Computing Group Inc."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20933"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20945"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-60056-z"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20290"},{"issue":"1","key":"e_1_2_9_26_1","article-title":"Antechamber: An Accessory Software Package for Molecular Mechanical Calculations","volume":"222","author":"Wang J.","year":"2001","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp003020w"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/comjnl\/6.2.163"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.464397"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct400341p"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.4172\/2161-0398.1000166"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2020.104185"}],"container-title":["Proteins: Structure, Function, and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prot.70055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T19:26:56Z","timestamp":1767814016000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prot.70055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/prot.70055"],"URL":"https:\/\/doi.org\/10.1002\/prot.70055","archive":["Portico"],"relation":{},"ISSN":["0887-3585","1097-0134"],"issn-type":[{"value":"0887-3585","type":"print"},{"value":"1097-0134","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,17]]},"assertion":[{"value":"2025-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}