{"entity": "researcher", "timestamp": "2026-07-22T16:18:14.923Z", "family": "von Delft", "given": "Frank", "initials": "F", "orcid": "0000-0003-0378-0017", "affiliations": ["Diamond Light Source, Didcot, United Kingdom.", "Structural Genomics Consortium, University of Oxford, Oxford, United Kingdom.", "Department of Biochemistry, University of Johannesburg, Johannesburg, South Africa."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/51e35baa89fe49ada5a9dcbc2c2e1e20.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/51e35baa89fe49ada5a9dcbc2c2e1e20"}}, "publications": [{"entity": "publication", "iuid": "fbac514e63244e01a9b3cfe502e173fe", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fbac514e63244e01a9b3cfe502e173fe.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fbac514e63244e01a9b3cfe502e173fe"}}, "title": "An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.", "authors": [{"family": "Keedy", "given": "Daniel A", "initials": "DA", "orcid": "0000-0002-9184-7586", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7fd571647a0e4ba9a85a1d339765f0c4.json"}}, {"family": "Hill", "given": "Zachary B", "initials": "ZB"}, {"family": "Biel", "given": "Justin T", "initials": "JT", "orcid": "0000-0002-0935-8362", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/884e784334ee4e67b1a985f90ef32821.json"}}, {"family": "Kang", "given": "Emily", "initials": "E"}, {"family": "Rettenmaier", "given": "T Justin", "initials": "TJ"}, {"family": "Brand\u00e3o-Neto", "given": "Jos\u00e9", "initials": "J", "orcid": "0000-0001-6015-320X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8692b60d7100483fa2fe0ecdc908f77b.json"}}, {"family": "Pearce", "given": "Nicholas M", "initials": "NM", "orcid": "0000-0002-6693-8603", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/07d6d5de91cc4120b2bf996ca578a13e.json"}}, {"family": "von Delft", "given": "Frank", "initials": "F", "orcid": "0000-0003-0378-0017", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51e35baa89fe49ada5a9dcbc2c2e1e20.json"}}, {"family": "Wells", "given": "James A", "initials": "JA", "orcid": "0000-0001-8267-5519", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f0c1fc2f2b584824bd489884424e333c.json"}}, {"family": "Fraser", "given": "James S", "initials": "JS", "orcid": "0000-0002-5080-2859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c95b7a3dcf1545ff87da0c64abdd0f68.json"}}], "type": "journal article", "published": "2018-06-07", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "7", "issn-l": "2050-084X"}, "abstract": "Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here, we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small-molecule fragment soaks. New modeling approaches reveal 'hidden' low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function.", "doi": "10.7554/eLife.36307", "pmid": "29877794", "labels": {"Nicholas Pearce": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC6039181"}, {"db": "pii", "key": "36307"}], "notes": [], "created": "2022-12-05T18:57:35.912Z", "modified": "2022-12-05T18:57:36.084Z"}, {"entity": "publication", "iuid": "f079c771c50442d1ac7072c0a6d77bd8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f079c771c50442d1ac7072c0a6d77bd8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f079c771c50442d1ac7072c0a6d77bd8"}}, "title": "A multi-crystal method for extracting obscured crystallographic states from conventionally uninterpretable electron density.", "authors": [{"family": "Pearce", "given": "Nicholas M", "initials": "NM"}, {"family": "Krojer", "given": "Tobias", "initials": "T"}, {"family": "Bradley", "given": "Anthony R", "initials": "AR"}, {"family": "Collins", "given": "Patrick", "initials": "P", "orcid": "0000-0002-6265-9922", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/67ac751ea9d9407db6de2b5ace3a2c22.json"}}, {"family": "Nowak", "given": "Rados\u0142aw P", "initials": "RP"}, {"family": "Talon", "given": "Romain", "initials": "R"}, {"family": "Marsden", "given": "Brian D", "initials": "BD"}, {"family": "Kelm", "given": "Sebastian", "initials": "S"}, {"family": "Shi", "given": "Jiye", "initials": "J"}, {"family": "Deane", "given": "Charlotte M", "initials": "CM", "orcid": "0000-0003-1388-2252", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a6e9c69dd1dc47bfad3b72dccfb836c0.json"}}, {"family": "von Delft", "given": "Frank", "initials": "F", "orcid": "0000-0003-0378-0017", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51e35baa89fe49ada5a9dcbc2c2e1e20.json"}}], "type": "journal article", "published": "2017-04-24", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "8", "pages": "15123", "issn-l": "2041-1723"}, "abstract": "In macromolecular crystallography, the rigorous detection of changed states (for example, ligand binding) is difficult unless signal is strong. Ambiguous ('weak' or 'noisy') density is experimentally common, since molecular states are generally only fractionally present in the crystal. Existing methodologies focus on generating maximally accurate maps whereby minor states become discernible; in practice, such map interpretation is disappointingly subjective, time-consuming and methodologically unsound. Here we report the PanDDA method, which automatically reveals clear electron density for the changed state-even from inaccurate maps-by subtracting a proportion of the confounding 'ground state'; changed states are objectively identified from statistical analysis of density distributions. The method is completely general, implying new best practice for all changed-state studies, including the routine collection of multiple ground-state crystals. More generally, these results demonstrate: the incompleteness of atomic models; that single data sets contain insufficient information to model them fully; and that accuracy requires further map-deconvolution approaches.", "doi": "10.1038/ncomms15123", "pmid": "28436492", "labels": {"Nicholas Pearce": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC5413968"}, {"db": "pii", "key": "ncomms15123"}], "notes": [], "created": "2022-12-05T18:57:43.605Z", "modified": "2022-12-05T18:57:43.661Z"}]}