{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vu QV"],"funding":["NIGMS NIH HHS"],"pagination":["eadt8974"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12333692"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(32)"],"pubmed_abstract":["Several mechanisms are known to cause monomeric protein misfolding. Coarse-grained simulations have predicted an additional mechanism exists involving off-pathway, noncovalent lasso entanglements, which are long-lived kinetic traps and structurally resemble the native state. Here, we examine whether such misfolded states occur in long-timescale, all-atom folding simulations of ubiquitin and λ-repressor. We find that these entangled misfolded states are populated in higher-resolution models. However, because of the small size of ubiquitin and λ-repressor, these states are short-lived. In contrast, coarse-grained simulations of a larger protein, IspE, predict that it populates long-lived misfolded states. Using an Arrhenius extrapolation applied to all-atom simulations, we estimate that thes"],"journal":["Science advances"],"pubmed_title":["Non-native entanglement protein misfolding observed in all-atom simulations and supported by experimental structural ensembles."],"pmcid":["PMC12333692"],"funding_grant_id":["DP2 GM140926","R35 GM124818"],"pubmed_authors":["Jiang Y","Xia Y","Sharma P","Sitarik I","Li MS","Vu QV","Fried SD","O'Brien EP","Yadav D","Song H"],"additional_accession":[]},"is_claimable":false,"name":"Non-native entanglement protein misfolding observed in all-atom simulations and supported by experimental structural ensembles.","description":"Several mechanisms are known to cause monomeric protein misfolding. Coarse-grained simulations have predicted an additional mechanism exists involving off-pathway, noncovalent lasso entanglements, which are long-lived kinetic traps and structurally resemble the native state. Here, we examine whether such misfolded states occur in long-timescale, all-atom folding simulations of ubiquitin and λ-repressor. We find that these entangled misfolded states are populated in higher-resolution models. However, because of the small size of ubiquitin and λ-repressor, these states are short-lived. In contrast, coarse-grained simulations of a larger protein, IspE, predict that it populates long-lived misfolded states. Using an Arrhenius extrapolation applied to all-atom simulations, we estimate that thes","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-06-03T07:01:26.602Z","creation":"2026-04-25T03:21:39.587Z"},"accession":"S-EPMC12333692","cross_references":{"pubmed":["40779622"],"doi":["10.1126/sciadv.adt8974"]}}