{"entity": "researcher", "timestamp": "2026-08-20T20:37:31.782Z", "family": "Karlsson", "given": "Emelia", "initials": "E", "orcid": "0009-0005-4878-964X", "affiliations": ["SciLifeLab, Department of Biochemistry and Biophysics, Stockholm University, Tomtebodav\u00e4gen 23, Solna, 17165 Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/08a1be310cbe486895961fd1c757404d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/08a1be310cbe486895961fd1c757404d"}}, "publications": [{"entity": "publication", "iuid": "38f6eb0690144d35b1585e0d75b478b1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/38f6eb0690144d35b1585e0d75b478b1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/38f6eb0690144d35b1585e0d75b478b1"}}, "title": "Discovering cryptic pocket opening and binding of a stimulant derivative in a vestibular site of the 5-HT3A receptor.", "authors": [{"family": "Haloi", "given": "Nandan", "initials": "N", "orcid": "0000-0003-3542-333X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a499486a86ba4df7a27d26dad6222b47.json"}}, {"family": "Karlsson", "given": "Emelia", "initials": "E", "orcid": "0009-0005-4878-964X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/08a1be310cbe486895961fd1c757404d.json"}}, {"family": "Delarue", "given": "Marc", "initials": "M", "orcid": "0000-0003-0723-8102", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ee0e290455aa46c5a3a7d9f0ce226dcf.json"}}, {"family": "Howard", "given": "Rebecca J", "initials": "RJ", "orcid": "0000-0003-2049-3378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce04593b5b24aaa8978fda1447dd0bf.json"}}, {"family": "Lindahl", "given": "Erik", "initials": "E", "orcid": "0000-0002-2734-2794", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9eb30fa60f9b4b95842ac9d9f3a0eaa9.json"}}], "type": "journal article", "published": "2025-04-11", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "11", "issue": "15", "pages": "eadr0797", "issn-l": "2375-2548"}, "abstract": "A diverse set of modulators, including stimulants and anesthetics, regulates ion channel function in our nervous system. However, structures of ligand-bound complexes can be difficult to capture by experimental methods, particularly when binding is dynamic. Here, we used computational methods and electrophysiology to identify a possible bound state of a modulatory stimulant derivative in a cryptic vestibular pocket of a mammalian serotonin-3 receptor. We first applied a molecular dynamics simulation-based goal-oriented adaptive sampling method to identify possible open-pocket conformations, followed by Boltzmann docking that combines traditional docking with Markov state modeling. Clustering and analysis of stability and accessibility of docked poses supported a preferred binding site; we further validated this site by mutagenesis and electrophysiology, suggesting a mechanism of potentiation by stabilizing intersubunit contacts. Given the pharmaceutical relevance of serotonin-3 receptors in emesis, psychiatric, and gastrointestinal diseases, characterizing relatively unexplored modulatory sites such as these could open valuable avenues to understanding conformational cycling and designing state-dependent drugs.", "doi": "10.1126/sciadv.adr0797", "pmid": "40215320", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11988449"}], "notes": [], "created": "2026-08-20T11:58:57.705Z", "modified": "2026-08-20T11:58:57.859Z"}]}