{"entity": "publication", "iuid": "1f3cd2186fb74306bda2da41ac451ef0", "timestamp": "2026-09-03T05:35:07.804Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1f3cd2186fb74306bda2da41ac451ef0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1f3cd2186fb74306bda2da41ac451ef0"}}, "title": "Automated simulation-based membrane protein refinement into cryo-EM data.", "authors": [{"family": "Yvonnesdotter", "given": "Linnea", "initials": "L"}, {"family": "Rov\u0161nik", "given": "Ur\u0161ka", "initials": "U"}, {"family": "Blau", "given": "Christian", "initials": "C"}, {"family": "Lycksell", "given": "Marie", "initials": "M"}, {"family": "Howard", "given": "Rebecca Joy", "initials": "RJ"}, {"family": "Lindahl", "given": "Erik", "initials": "E"}], "type": "journal article", "published": "2023-07-11", "journal": {"title": "Biophys. J.", "issn": "1542-0086", "volume": "122", "issue": "13", "pages": "2773-2781", "issn-l": "0006-3495"}, "abstract": "The resolution revolution has increasingly enabled single-particle cryogenic electron microscopy (cryo-EM) reconstructions of previously inaccessible systems, including membrane proteins-a category that constitutes a disproportionate share of drug targets. We present a protocol for using density-guided molecular dynamics simulations to automatically refine atomistic models into membrane protein cryo-EM maps. Using adaptive force density-guided simulations as implemented in the GROMACS molecular dynamics package, we show how automated model refinement of a membrane protein is achieved without the need to manually tune the fitting force ad hoc. We also present selection criteria to choose the best-fit model that balances stereochemistry and goodness of fit. The proposed protocol was used to refine models into a new cryo-EM density of the membrane protein maltoporin, either in a lipid bilayer or detergent micelle, and we found that results do not substantially differ from fitting in solution. Fitted structures satisfied classical model-quality metrics and improved the quality and the model-to-map correlation of the x-ray starting structure. Additionally, the density-guided fitting in combination with generalized orientation-dependent all-atom potential was used to correct the pixel-size estimation of the experimental cryo-EM density map. This work demonstrates the applicability of a straightforward automated approach to fitting membrane protein cryo-EM densities. Such computational approaches promise to facilitate rapid refinement of proteins under different conditions or with various ligands present, including targets in the highly relevant superfamily of membrane proteins.", "doi": "10.1016/j.bpj.2023.05.033", "pmid": "37277992", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10397807"}, {"db": "pii", "key": "S0006-3495(23)00367-3"}], "notes": [], "created": "2026-08-20T06:45:01.000Z", "modified": "2026-08-20T06:45:01.016Z"}