{"entity": "researcher", "timestamp": "2026-08-20T20:53:54.480Z", "family": "Lidbrink", "given": "Samuel Eriksson", "initials": "SE", "orcid": "0009-0008-4290-0177", "affiliations": [], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/128b592528b141618ad70079911ca8b8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/128b592528b141618ad70079911ca8b8"}}, "publications": [{"entity": "publication", "iuid": "faece4f720a34ae6b7db97dc9981c5ae", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/faece4f720a34ae6b7db97dc9981c5ae.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/faece4f720a34ae6b7db97dc9981c5ae"}}, "title": "Resolving the conformational ensemble of a membrane protein by integrating small-angle scattering with AlphaFold.", "authors": [{"family": "Lidbrink", "given": "Samuel Eriksson", "initials": "SE", "orcid": "0009-0008-4290-0177", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/128b592528b141618ad70079911ca8b8.json"}}, {"family": "Howard", "given": "Rebecca J", "initials": "RJ"}, {"family": "Haloi", "given": "Nandan", "initials": "N", "orcid": "0000-0003-3542-333X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a499486a86ba4df7a27d26dad6222b47.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": "2025-06-00", "journal": {"title": "PLoS Comput Biol", "issn": "1553-7358", "volume": "21", "issue": "6", "pages": "e1013187", "issn-l": "1553-734X"}, "abstract": "The function of a protein is enabled by its conformational landscape. For non-rigid proteins, a complete characterization of this landscape requires understanding the protein's structure in all functional states, the stability of these states under target conditions, and the transition pathways between them. Several strategies have recently been developed to drive the machine learning algorithm AlphaFold2 (AF) to sample multiple conformations, but it is more challenging to a priori predict what states are stabilized in particular conditions and how the transition occurs. Here, we combine AF sampling with small-angle scattering curves to obtain a weighted conformational ensemble of functional states under target environmental conditions. We apply this to the pentameric ion channel GLIC using small-angle neutron scattering (SANS) curves, and identify apparent closed and open states. By comparing experimental SANS data under resting and activating conditions, we can quantify the subpopulation of closed channels that open upon activation, matching both experiments and extensive simulation sampling using Markov state models. The predicted closed and open states closely resemble crystal structures determined under resting and activating conditions respectively, and project to predicted basins in free energy landscapes calculated from the Markov state models. Further, without using any structural information, the AF sampling also correctly captures intermediate conformations and projects onto the transition pathway resolved in the extensive sampling. This combination of machine learning algorithms and low-dimensional experimental data appears to provide an efficient way to predict not only stable conformations but also accurately sample the transition pathways several orders of magnitude faster than simulation-based sampling.", "doi": "10.1371/journal.pcbi.1013187", "pmid": "40577488", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12251176"}, {"db": "pii", "key": "PCOMPBIOL-D-24-01584"}], "notes": [], "created": "2026-08-20T12:43:21.781Z", "modified": "2026-08-20T12:43:21.877Z"}, {"entity": "publication", "iuid": "057169e7dfd44345b3397ed28918f1f5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/057169e7dfd44345b3397ed28918f1f5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/057169e7dfd44345b3397ed28918f1f5"}}, "title": "Adaptive sampling-based structural prediction reveals opening of a GABAA receptor through the \u03b1\u03b2 interface.", "authors": [{"family": "Haloi", "given": "Nandan", "initials": "N", "orcid": "0000-0003-3542-333X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a499486a86ba4df7a27d26dad6222b47.json"}}, {"family": "Eriksson Lidbrink", "given": "Samuel", "initials": "S", "orcid": "0009-0008-4290-0177", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/128b592528b141618ad70079911ca8b8.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": "2025-01-10", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "11", "issue": "2", "pages": "eadq3788", "issn-l": "2375-2548"}, "abstract": "\u03b3-Aminobutyric acid type A (GABAA) receptors are ligand-gated ion channels in the central nervous system with largely inhibitory function. Despite being a target for drugs including general anesthetics and benzodiazepines, experimental structures have yet to capture an open state of classical synaptic \u03b11\u03b22\u03b32 GABAA receptors. Here, we use a goal-oriented adaptive sampling strategy in molecular dynamics simulations followed by Markov state modeling to capture an energetically stable putative open state of the receptor. The model conducts chloride ions with comparable conductance as in electrophysiology measurements. Relative to experimental structures, our open model is relatively expanded at both the cytoplasmic (-2') and central (9') gates, coordinated with distinctive rearrangements at the transmembrane \u03b1\u03b2 subunit interface. Consistent with previous experiments, targeted substitutions disrupting interactions at this interface slowed the open-to-desensitized transition rate. This work demonstrates the capacity of advanced simulation techniques to investigate a computationally and experimentally plausible functionally critical of a complex membrane protein yet to be resolved by experimental methods.", "doi": "10.1126/sciadv.adq3788", "pmid": "39772677", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11708891"}], "notes": [], "created": "2026-08-20T11:58:55.855Z", "modified": "2026-08-20T11:58:55.936Z"}, {"entity": "publication", "iuid": "d75f1562bf374f0d9ca0883df4a6878e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d75f1562bf374f0d9ca0883df4a6878e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d75f1562bf374f0d9ca0883df4a6878e"}}, "title": "Resolving the conformational ensemble of a membrane protein by integrating small-angle scattering with AlphaFold", "authors": [{"family": "Lidbrink", "given": "Samuel Eriksson", "initials": "SE", "orcid": "0009-0008-4290-0177", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/128b592528b141618ad70079911ca8b8.json"}}, {"family": "Howard", "given": "Rebecca", "initials": "R", "orcid": "0000-0003-2049-3378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce04593b5b24aaa8978fda1447dd0bf.json"}}, {"family": "Haloi", "given": "Nandan", "initials": "N", "orcid": "0000-0003-3542-333X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a499486a86ba4df7a27d26dad6222b47.json"}}, {"family": "Lindahl", "given": "Erik", "initials": "E", "orcid": "0000-0002-2734-2794", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9eb30fa60f9b4b95842ac9d9f3a0eaa9.json"}}], "type": "posted-content", "published": "2024-09-07", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2024.09.05.611464", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:58:21.507Z", "modified": "2026-08-20T10:58:21.593Z"}]}