{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:07:39Z","timestamp":1788584859992,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pbio.3003731","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000}}],"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32401019"],"award-info":[{"award-number":["32401019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52388101"],"award-info":[{"award-number":["52388101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471254"],"award-info":[{"award-number":["32471254"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430027"],"award-info":[{"award-number":["82430027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32501293"],"award-info":[{"award-number":["32501293"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007162","name":"Guangdong Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2024A1515010991"],"award-info":[{"award-number":["2024A1515010991"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007162","name":"Guangdong Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2024TQ08A721"],"award-info":[{"award-number":["2024TQ08A721"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20230807114207016"],"award-info":[{"award-number":["JCYJ20230807114207016"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20240813113600001"],"award-info":[{"award-number":["JCYJ20240813113600001"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Medical Research Fund, Youth Project","award":["A2403008"],"award-info":[{"award-number":["A2403008"]}]},{"name":"Kobilka Institute of Innovative Drug Discovery at the Chinese University of Hong Kong, Shenzhen"},{"name":"Kobilka Institute of Innovative Drug Discovery at the Chinese University of Hong Kong, Shenzhen"}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>The human glucose-6-phosphate transporter (G6PT\/SLC37A4) mediates the translocation of glucose-6-phosphate (G6P) from the cytoplasm into the endoplasmic reticulum, a process essential for glucose production and the maintenance of blood glucose homeostasis between meals. Dysfunction of G6PT causes glycogen storage disease type Ib (GSD-Ib), a severe metabolic disorder characterized by hypoglycemia, hepatomegaly, and neutropenia. Despite its physiological and clinical significance, the structural basis of G6P recognition and the molecular mechanisms underlying GSD-Ib have remained elusive. Here, we present cryo-electron microscopy structures of human G6PT, revealing a monomer in an outward-open state at 3.1 \u00c5 and a homodimeric assembly in a face-to-face topology at 3.3 \u00c5. By combining computational modeling of the G6P\u2013G6PT complexes with functional characterization, we have uncovered the key molecular elements that govern the alternating-access mechanism: an electropositive substrate-binding pocket tailored for phosphorylated sugars; conserved aromatic residues that seal the cytosolic gate; and a dynamic inter-domain salt bridge that regulates the conformational transition. Our work provides fundamental insights into the transport cycle of the organophosphate:phosphate antiporter (OPA) family, offers a framework for interpreting GSD-Ib pathology at the molecular level, and establishes a foundation for advancing the mechanistic understanding of the human SLC37 family.<\/jats:p>","DOI":"10.1371\/journal.pbio.3003731","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T17:28:28Z","timestamp":1774891708000},"page":"e3003731","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Structures of the human glucose-6-phosphate transporter provide insights into its transport cycle and substrate recognition"],"prefix":"10.1371","volume":"24","author":[{"given":"Wanqin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haizhan","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingchuan","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuye","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geshu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3658-272X","authenticated-orcid":true,"given":"Hongli","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9158-7227","authenticated-orcid":true,"given":"Xue","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"pbio.3003731.ref001","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/B978-0-12-800223-0.00010-4","article-title":"The SLC37 family of sugar-phosphate\/phosphate exchangers","volume":"73","author":"JY Chou","year":"2014","journal-title":"Curr Top Membr"},{"key":"pbio.3003731.ref002","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.mam.2012.05.010","article-title":"The SLC37 family of phosphate-linked sugar phosphate antiporters","volume":"34","author":"JY Chou","year":"2013","journal-title":"Mol Aspects Med"},{"issue":"9","key":"pbio.3003731.ref003","article-title":"SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters","volume":"6","author":"C-J Pan","year":"2011","journal-title":"PLoS One"},{"issue":"20","key":"pbio.3003731.ref004","doi-asserted-by":"crossref","first-page":"13865","DOI":"10.1074\/jbc.274.20.13865","article-title":"Transmembrane topology of human glucose 6-phosphate transporter","volume":"274","author":"CJ Pan","year":"1999","journal-title":"J Biol Chem"},{"issue":"1","key":"pbio.3003731.ref005","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ymgme.2008.10.005","article-title":"Structure-function study of the glucose-6-phosphate transporter, an eukaryotic antiporter deficient in glycogen storage disease type Ib","volume":"96","author":"C-J Pan","year":"2009","journal-title":"Mol Genet Metab"},{"issue":"5","key":"pbio.3003731.ref006","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1007\/s004390000404","article-title":"Human variant glucose-6-phosphate transporter is active in microsomal transport","volume":"107","author":"B Lin","year":"2000","journal-title":"Hum Genet"},{"issue":"6","key":"pbio.3003731.ref007","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/wmts.98","article-title":"The sugar phosphate\/phosphate exchanger family SLC37","volume":"2","author":"C Olcese","year":"2013","journal-title":"WIREs Membr Transp Signal"},{"key":"pbio.3003731.ref008","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3389\/fchem.2018.00122","article-title":"The Physiopathological role of the exchangers belonging to the SLC37 family","volume":"6","author":"AR Cappello","year":"2018","journal-title":"Front Chem"},{"issue":"2","key":"pbio.3003731.ref009","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/BF01732001","article-title":"On the involvement of a glucose 6-phosphate transport system in the function of microsomal glucose 6-phosphatase","volume":"6","author":"WJ Arion","year":"1975","journal-title":"Mol Cell Biochem"},{"issue":"9","key":"pbio.3003731.ref010","doi-asserted-by":"crossref","first-page":"5532","DOI":"10.1074\/jbc.274.9.5532","article-title":"Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b","volume":"274","author":"H Hiraiwa","year":"1999","journal-title":"J Biol Chem"},{"issue":"2","key":"pbio.3003731.ref011","doi-asserted-by":"crossref","DOI":"10.1002\/pdi3.3","article-title":"Glycogen storage disease type I: genetic etiology, clinical manifestations, and conventional and gene therapies","volume":"1","author":"J Zhong","year":"2023","journal-title":"Pediatr Discov"},{"issue":"12","key":"pbio.3003731.ref012","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3390\/metabo9120282","article-title":"Glucose-6 phosphate, a central hub for liver carbohydrate metabolism","volume":"9","author":"F Rajas","year":"2019","journal-title":"Metabolites"},{"issue":"5","key":"pbio.3003731.ref013","article-title":"Pathophysiology of the neutropenia of GSDIb and G6PC3 deficiency: origin, metabolism and elimination of 1,5-anhydroglucitol","volume":"48","author":"M Veiga-da-Cunha","year":"2025","journal-title":"J Inherit Metab Dis"},{"issue":"2","key":"pbio.3003731.ref014","doi-asserted-by":"crossref","DOI":"10.1016\/j.cmet.2020.11.016","article-title":"Neutrophils fuel effective immune responses through gluconeogenesis and glycogenesis","volume":"33","author":"P Sadiku","year":"2021","journal-title":"Cell Metab"},{"issue":"12","key":"pbio.3003731.ref015","doi-asserted-by":"crossref","first-page":"5704","DOI":"10.1182\/blood-2007-12-129114","article-title":"Neutrophil stress and apoptosis underlie myeloid dysfunction in glycogen storage disease type Ib","volume":"111","author":"SY Kim","year":"2008","journal-title":"Blood"},{"issue":"4","key":"pbio.3003731.ref016","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1073\/pnas.1816143116","article-title":"Failure to eliminate a phosphorylated glucose analog leads to neutropenia in patients with G6PT and G6PC3 deficiency","volume":"116","author":"M Veiga-da-Cunha","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"pbio.3003731.ref017","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nrendo.2010.189","article-title":"Glycogen storage disease type I and G6Pase-\u03b2 deficiency: etiology and therapy","volume":"6","author":"JY Chou","year":"2010","journal-title":"Nat Rev Endocrinol"},{"issue":"19","key":"pbio.3003731.ref018","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1093\/hmg\/ddg263","article-title":"Impaired glucose homeostasis, neutrophil trafficking and function in mice lacking the glucose-6-phosphate transporter","volume":"12","author":"L-Y Chen","year":"2003","journal-title":"Hum Mol Genet"},{"issue":"2","key":"pbio.3003731.ref019","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2174\/1566524024605798","article-title":"Type I glycogen storage diseases: disorders of the glucose-6-phosphatase complex","volume":"2","author":"JY Chou","year":"2002","journal-title":"Curr Mol Med"},{"key":"pbio.3003731.ref020","article-title":"Defective neutrophil and monocyte functions in glycogen storage disease type Ib: a literature review","author":"R Gitzelmann","year":"1993","journal-title":"Eur J Pediatr"},{"issue":"1","key":"pbio.3003731.ref021","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/1873-3468.13666","article-title":"Glycogen storage disease type Ib: role of glucose-6-phosphate transporter in cell metabolism and function","volume":"594","author":"SW Sim","year":"2020","journal-title":"FEBS Lett"},{"issue":"44","key":"pbio.3003731.ref022","doi-asserted-by":"crossref","first-page":"34280","DOI":"10.1074\/jbc.M006439200","article-title":"Structural requirements for the stability and microsomal transport activity of the human glucose 6-phosphate transporter","volume":"275","author":"LY Chen","year":"2000","journal-title":"J Biol Chem"},{"issue":"25","key":"pbio.3003731.ref023","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1093\/hmg\/11.25.3199","article-title":"Structure-function analysis of the glucose-6-phosphate transporter deficient in glycogen storage disease type Ib","volume":"11","author":"L-Y Chen","year":"2002","journal-title":"Hum Mol Genet"},{"issue":"4","key":"pbio.3003731.ref024","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1007\/s00439-002-0903-3","article-title":"The signature motif in human glucose-6-phosphate transporter is essential for microsomal transport of glucose-6-phosphate","volume":"112","author":"C-J Pan","year":"2003","journal-title":"Hum Genet"},{"issue":"4","key":"pbio.3003731.ref025","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ymgme.2008.08.005","article-title":"Functional analysis of mutations in the glucose-6-phosphate transporter that cause glycogen storage disease type Ib","volume":"95","author":"S-Y Chen","year":"2008","journal-title":"Mol Genet Metab"},{"key":"pbio.3003731.ref026","unstructured":"HGMD\u00ae gene result [cited 2025 October 11]. Available from: https:\/\/www.hgmd.cf.ac.uk\/ac\/gene.php?gene=SLC37A4"},{"issue":"8","key":"pbio.3003731.ref027","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.resmic.2004.05.016","article-title":"Glycerol-3-phosphate transporter of Escherichia coli: structure, function and regulation","volume":"155","author":"MJ Lemieux","year":"2004","journal-title":"Res Microbiol"},{"issue":"5633","key":"pbio.3003731.ref028","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1126\/science.1087619","article-title":"Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli","volume":"301","author":"Y Huang","year":"2003","journal-title":"Science"},{"issue":"2","key":"pbio.3003731.ref029","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.11.043","article-title":"Structural basis of human monocarboxylate transporter 1 inhibition by anti-cancer drug candidates","volume":"184","author":"N Wang","year":"2021","journal-title":"Cell"},{"issue":"7","key":"pbio.3003731.ref030","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/s41592-024-02304-8","article-title":"Data-driven regularization lowers the size barrier of cryo-EM structure determination","volume":"21","author":"D Kimanius","year":"2024","journal-title":"Nat Methods"},{"issue":"1","key":"pbio.3003731.ref031","doi-asserted-by":"crossref","first-page":"7822","DOI":"10.1038\/s41467-023-43555-x","article-title":"A minority of final stacks yields superior amplitude in single-particle cryo-EM","volume":"14","author":"J Zhu","year":"2023","journal-title":"Nat Commun"},{"issue":"7573","key":"pbio.3003731.ref032","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nature14655","article-title":"Molecular basis of ligand recognition and transport by glucose transporters","volume":"526","author":"D Deng","year":"2015","journal-title":"Nature"},{"issue":"17","key":"pbio.3003731.ref033","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1016\/j.jmb.2017.07.009","article-title":"A glimpse of membrane transport through structures-advances in the structural biology of the GLUT glucose transporters","volume":"429","author":"N Yan","year":"2017","journal-title":"J Mol Biol"},{"issue":"1","key":"pbio.3003731.ref034","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1038\/s41467-020-16334-1","article-title":"Cooperative transport mechanism of human monocarboxylate transporter 2","volume":"11","author":"B Zhang","year":"2020","journal-title":"Nat Commun"},{"issue":"7490","key":"pbio.3003731.ref035","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nature13074","article-title":"Crystal structure of the plant dual-affinity nitrate transporter NRT1.1","volume":"507","author":"J Sun","year":"2014","journal-title":"Nature"},{"issue":"1","key":"pbio.3003731.ref036","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1038\/s41467-025-58131-8","article-title":"Structural insights into thyroid hormone transporter MCT8","volume":"16","author":"J Tan","year":"2025","journal-title":"Nat Commun"},{"issue":"5","key":"pbio.3003731.ref037","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adz8234","article-title":"Structural insight into the glucose-6-phosphate transport by G6PT1 and inhibition mechanism of CGA","volume":"12","author":"Q Chen","year":"2026","journal-title":"Sci Adv"},{"issue":"1","key":"pbio.3003731.ref038","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41594-025-01711-5","article-title":"Structural basis of G6P\/Pi transport and inhibition in SLC37A4","volume":"33","author":"D Zhou","year":"2026","journal-title":"Nat Struct Mol Biol"},{"issue":"1","key":"pbio.3003731.ref039","doi-asserted-by":"crossref","first-page":"11441","DOI":"10.1038\/s41467-025-66386-4","article-title":"Structures of human glucose-6-phosphate transporter reveal reciprocal antiport mechanism driving glucose-6-phosphate and inorganic phosphate exchange","volume":"16","author":"Q Wang","year":"2025","journal-title":"Nat Commun"},{"issue":"4","key":"pbio.3003731.ref040","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.jmb.2008.03.029","article-title":"Salt-bridge dynamics control substrate-induced conformational change in the membrane transporter GlpT","volume":"378","author":"CJ Law","year":"2008","journal-title":"J Mol Biol"},{"issue":"8016","key":"pbio.3003731.ref041","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"J Abramson","year":"2024","journal-title":"Nature"},{"issue":"1","key":"pbio.3003731.ref042","doi-asserted-by":"crossref","first-page":"9420","DOI":"10.1038\/s41467-025-64464-1","article-title":"Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT","volume":"16","author":"Z Xia","year":"2025","journal-title":"Nat Commun"},{"issue":"7872","key":"pbio.3003731.ref043","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/s41586-021-03782-y","article-title":"Structure and mechanism of blood-brain-barrier lipid transporter MFSD2A","volume":"596","author":"CAP Wood","year":"2021","journal-title":"Nature"},{"issue":"3","key":"pbio.3003731.ref044","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","article-title":"RELION: implementation of a Bayesian approach to cryo-EM structure determination","volume":"180","author":"SHW Scheres","year":"2012","journal-title":"J Struct Biol"},{"issue":"3","key":"pbio.3003731.ref045","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nmeth.4169","article-title":"cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination","volume":"14","author":"A Punjani","year":"2017","journal-title":"Nat Methods"},{"issue":"1","key":"pbio.3003731.ref046","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: structure visualization for researchers, educators, and developers","volume":"30","author":"EF Pettersen","year":"2021","journal-title":"Protein Sci"},{"key":"pbio.3003731.ref047","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"P Emsley","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"pbio.3003731.ref048","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","article-title":"Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix","volume":"75","author":"D Liebschner","year":"2019","journal-title":"Acta Crystallogr D Struct Biol"},{"key":"pbio.3003731.ref049","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gky309","article-title":"MOLEonline: a web-based tool for analyzing channels, tunnels and pores (2018 update)","volume":"46","author":"L Pravda","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"22","key":"pbio.3003731.ref050","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","article-title":"CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice","volume":"22","author":"JD Thompson","year":"1994","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"pbio.3003731.ref051","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2\u2014a multiple sequence alignment editor and analysis workbench","volume":"25","author":"AM Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"pbio.3003731.ref052","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkr703","article-title":"OPM database and PPM web server: resources for positioning of proteins in membranes","volume":"40","author":"MA Lomize","year":"2012","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pbio.3003731.ref053","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bpj.2009.04.013","article-title":"CHARMM-GUI membrane builder for mixed bilayers and its application to yeast membranes","volume":"97","author":"S Jo","year":"2009","journal-title":"Biophys J"},{"issue":"10","key":"pbio.3003731.ref054","doi-asserted-by":"crossref","first-page":"5192","DOI":"10.1021\/acs.jcim.1c00770","article-title":"CHARMM-GUI membrane builder for lipid nanoparticles with ionizable cationic lipids and PEGylated lipids","volume":"61","author":"S Park","year":"2021","journal-title":"J Chem Inf Model"},{"key":"pbio.3003731.ref055","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"MJ Abraham","year":"2015","journal-title":"SoftwareX"},{"issue":"1","key":"pbio.3003731.ref056","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: an improved force field for folded and intrinsically disordered proteins","volume":"14","author":"J Huang","year":"2017","journal-title":"Nat Methods"},{"issue":"2","key":"pbio.3003731.ref057","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"WL Jorgensen","year":"1983","journal-title":"J Chem Phys"},{"issue":"16","key":"pbio.3003731.ref058","doi-asserted-by":"crossref","first-page":"9478","DOI":"10.1021\/acs.chemrev.9b00055","article-title":"End-point binding free energy calculation with MM\/PBSA and MM\/GBSA: strategies and applications in drug design","volume":"119","author":"E Wang","year":"2019","journal-title":"Chem Rev"}],"updated-by":[{"DOI":"10.1371\/journal.pbio.3003731","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000}}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003731","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:52:21Z","timestamp":1775152341000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003731"}},"subtitle":[],"editor":[{"given":"Raimund","family":"Dutzler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":58,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3003731","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]}}}