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With ever-increasing resistance to currently deployed antimalarials, new targets and starting point compounds with novel mechanisms of action need to be identified. Here, we explore the antimalarial activity of the\n                    <jats:italic>Streptomyces sp<\/jats:italic>\n                    natural product, 5\u2032-\n                    <jats:italic>O<\/jats:italic>\n                    -sulfamoyl-2-chloroadenosine (dealanylascamycin, DACM) and compare it with the synthetic adenosine monophosphate (AMP) mimic, 5-\n                    <jats:italic>O<\/jats:italic>\n                    -sulfamoyladenosine (AMS). These nucleoside sulfamates exhibit potent inhibition of\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    growth with an efficacy comparable to that of the current front-line antimalarial, dihydroartemisinin. Exposure of\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    to DACM leads to inhibition of protein translation, driven by eIF2\u03b1 phosphorylation. We show that DACM targets multiple aminoacyl-tRNA synthetases (aaRSs), including the cytoplasmic aspartyl tRNA synthetase (AspRS). The mechanism involves hijacking of the reaction product, leading to the formation of a tightly bound inhibitory amino acid-sulfamate conjugate. We show that recombinant\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    and\n                    <jats:italic>P. vivax<\/jats:italic>\n                    AspRS are susceptible to hijacking by DACM and AMS, generating Asp-DACM and Asp-AMS adducts that stabilize these proteins. By contrast, human AspRS appears less susceptible to hijacking. X-ray crystallography reveals that apo\n                    <jats:italic>P. vivax<\/jats:italic>\n                    AspRS exhibits a stabilized flipping loop over the active site that is poised to bind substrates. By contrast, human AspRS exhibits disorder in an extended region around the flexible flipping loop as well as in a loop in motif II. These structural differences may underpin the decreased susceptibility of human AspRS to reaction-hijacking by DACM and AMS. Our work reveals\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    AspRS as a promising antimalarial target and highlights structural features that underpin differences in the susceptibility of aaRSs to reaction hijacking inhibition.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013057","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T15:31:30Z","timestamp":1751988690000},"page":"e1013057","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Natural product-mediated reaction hijacking mechanism validates Plasmodium aspartyl-tRNA synthetase as an antimalarial drug target"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8750-0187","authenticated-orcid":true,"given":"Nutpakal","family":"Ketprasit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wei","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek Kumar","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogavel","family":"Manickam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Khandokar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Con","family":"Dogovski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Hilko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"Morton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie C.","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Leeming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bagale","family":"Siddharam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J.","family":"Shami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushpangadan Indira","family":"Pradeepkumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Panjikar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally-Ann","family":"Poulsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D. W.","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3305-0034","authenticated-orcid":true,"given":"Amit","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9910-0199","authenticated-orcid":true,"given":"Leann","family":"Tilley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7003-4677","authenticated-orcid":true,"given":"Stanley C.","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ppat.1013057.ref001","volume-title":"WHO World Malaria Report 2024","author":"World Health 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Bloch","year":"1971","journal-title":"Biochemistry"},{"issue":"6","key":"ppat.1013057.ref023","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1021\/np501015m","article-title":"Natural product primary sulfonamides and primary sulfamates","volume":"78","author":"P Mujumdar","year":"2015","journal-title":"J Nat Prod"},{"issue":"17","key":"ppat.1013057.ref024","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1016\/j.bmcl.2018.04.038","article-title":"Synthesis, structure and bioactivity of primary sulfamate-containing natural products","volume":"28","author":"P Mujumdar","year":"2018","journal-title":"Bioorg Med Chem Lett"},{"issue":"41","key":"ppat.1013057.ref025","doi-asserted-by":"crossref","first-page":"10621","DOI":"10.1002\/chem.202100337","article-title":"Molecular tools for the study of ADP-Ribosylation: a unified and versatile method to synthesise native Mono-ADP-Ribosylated peptides","volume":"27","author":"J Voorneveld","year":"2021","journal-title":"Chemistry"},{"issue":"2","key":"ppat.1013057.ref026","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0040-4020(01)89967-1","article-title":"A facile synthesis of ascamycin and related analogues","volume":"43","author":"J Castro-Pichel","year":"1987","journal-title":"Tetrahedron"},{"issue":"21","key":"ppat.1013057.ref027","doi-asserted-by":"crossref","first-page":"9703","DOI":"10.1021\/acs.jmedchem.9b01131","article-title":"Structure-guided enhancement of selectivity of chemical probe inhibitors targeting bacterial seryl-tRNA synthetase","volume":"62","author":"R Cain","year":"2019","journal-title":"J Med Chem"},{"issue":"18","key":"ppat.1013057.ref028","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/S0264-410X(99)00444-2","article-title":"Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers","volume":"18","author":"G Lawrence","year":"2000","journal-title":"Vaccine"},{"issue":"3","key":"ppat.1013057.ref029","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/cyto.a.20856","article-title":"Dual labeling with a far red probe permits analysis of growth and oxidative stress in P. falciparum-infected erythrocytes","volume":"77","author":"Y Fu","year":"2010","journal-title":"Cytometry A"},{"key":"ppat.1013057.ref030","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/ncomms1558","article-title":"Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum","volume":"2","author":"L Solyakov","year":"2011","journal-title":"Nat Commun"},{"issue":"1","key":"ppat.1013057.ref031","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1038\/s41467-018-06221-1","article-title":"Artemisinin kills malaria parasites by damaging proteins and inhibiting the proteasome","volume":"9","author":"JL Bridgford","year":"2018","journal-title":"Nat Commun"},{"issue":"2","key":"ppat.1013057.ref032","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1073\/pnas.1111561108","article-title":"Imaging protein synthesis in cells and tissues with an alkyne analog of puromycin","volume":"109","author":"J Liu","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"ppat.1013057.ref033","article-title":"Dimeric artesunate glycerophosphocholine conjugate nano-assemblies as slow-release antimalarials to overcome Kelch 13 mutant artemisinin resistance","volume":"66","author":"Y Du","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"ppat.1013057.ref034","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1021\/jm020406h","article-title":"Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine","volume":"46","author":"AN Jain","year":"2003","journal-title":"J Med Chem"},{"issue":"6289","key":"ppat.1013057.ref035","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/347203a0","article-title":"Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs","volume":"347","author":"G Eriani","year":"1990","journal-title":"Nature"},{"issue":"28","key":"ppat.1013057.ref036","doi-asserted-by":"crossref","first-page":"18893","DOI":"10.1074\/jbc.M109.015297","article-title":"Plasmodial aspartyl-tRNA synthetases and peculiarities in Plasmodium falciparum","volume":"284","author":"T Bour","year":"2009","journal-title":"J Biol Chem"},{"issue":"10","key":"ppat.1013057.ref037","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1093\/emboj\/19.10.2371","article-title":"A domain in the N-terminal extension of class IIb eukaryotic aminoacyl-tRNA synthetases is important for tRNA binding","volume":"19","author":"M Frugier","year":"2000","journal-title":"EMBO J"},{"key":"ppat.1013057.ref038","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ymeth.2016.10.013","article-title":"Characterization of aminoacyl-tRNA synthetase stability and substrate interaction by differential scanning fluorimetry","volume":"113","author":"JA Abbott","year":"2017","journal-title":"Methods"},{"issue":"18","key":"ppat.1013057.ref039","doi-asserted-by":"crossref","first-page":"5290","DOI":"10.1093\/emboj\/20.18.5290","article-title":"The structure of an AspRS-tRNA(Asp) complex reveals a tRNA-dependent control mechanism","volume":"20","author":"L Moulinier","year":"2001","journal-title":"EMBO J"},{"issue":"17","key":"ppat.1013057.ref040","doi-asserted-by":"crossref","first-page":"5227","DOI":"10.1093\/emboj\/17.17.5227","article-title":"Crystal structure of aspartyl-tRNA synthetase from Pyrococcus kodakaraensis KOD: archaeon specificity and catalytic mechanism of adenylate formation","volume":"17","author":"E Schmitt","year":"1998","journal-title":"EMBO J"},{"issue":"22","key":"ppat.1013057.ref041","doi-asserted-by":"crossref","first-page":"6532","DOI":"10.1093\/emboj\/18.22.6532","article-title":"Synthesis of aspartyl-tRNA(Asp) in Escherichia coli--a snapshot of the second step","volume":"18","author":"S Eiler","year":"1999","journal-title":"EMBO J"},{"issue":"10","key":"ppat.1013057.ref042","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1002\/prot.24306","article-title":"Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex","volume":"81","author":"KR Kim","year":"2013","journal-title":"Proteins"},{"issue":"6416","key":"ppat.1013057.ref043","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/362181a0","article-title":"Yeast tRNA(Asp) recognition by its cognate class II aminoacyl-tRNA synthetase","volume":"362","author":"J Cavarelli","year":"1993","journal-title":"Nature"},{"issue":"5","key":"ppat.1013057.ref044","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/BF00166618","article-title":"The class II aminoacyl-tRNA synthetases and their active site: evolutionary conservation of an ATP binding site","volume":"40","author":"G Eriani","year":"1995","journal-title":"J Mol Evol"},{"issue":"5","key":"ppat.1013057.ref045","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1006\/jmbi.2000.3792","article-title":"Aspartyl tRNA-synthetase from Escherichia coli: flexibility and adaptability to the substrates","volume":"299","author":"B Rees","year":"2000","journal-title":"J Mol Biol"},{"key":"ppat.1013057.ref046","first-page":"716","article-title":"Nucleocidin, a new antibiotic with activity against Trypanosomes","author":"SO Thomas","year":"1956","journal-title":"Antibiot Annu"},{"issue":"4","key":"ppat.1013057.ref047","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1021\/ja01561a076","article-title":"The structure of nucleocidin. I","volume":"79","author":"CW Waller","year":"1957","journal-title":"J Am Chem Soc"},{"issue":"6","key":"ppat.1013057.ref048","doi-asserted-by":"crossref","first-page":"670","DOI":"10.7164\/antibiotics.37.670","article-title":"Ascamycin and dealanylascamycin, nucleoside antibiotics from Streptomyces sp","volume":"37","author":"K Isono","year":"1984","journal-title":"J Antibiot (Tokyo)"},{"issue":"5","key":"ppat.1013057.ref049","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S0021-9258(18)96807-9","article-title":"Inhibition of protein synthesis in vitro and in vivo by nucleocidin, an antitrypanosomal antibiotic","volume":"241","author":"JR Florini","year":"1966","journal-title":"J Biol Chem"},{"issue":"9","key":"ppat.1013057.ref050","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1016\/j.bbamcr.2014.04.006","article-title":"Keeping the eIF2 alpha kinase Gcn2 in check","volume":"1843","author":"BA Castilho","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"ppat.1013057.ref051","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/1475-2875-8-99","article-title":"PfeIK1, a eukaryotic initiation factor 2alpha kinase of the human malaria parasite Plasmodium falciparum, regulates stress-response to amino-acid starvation","volume":"8","author":"C Fennell","year":"2009","journal-title":"Malar J"},{"issue":"52","key":"ppat.1013057.ref052","doi-asserted-by":"crossref","first-page":"32937","DOI":"10.1016\/S0021-9258(20)30081-8","article-title":"Characterization of a novel N-terminal peptide in human aspartyl-tRNA synthetase. Roles in the transfer of aminoacyl-tRNA from aminoacyl-tRNA synthetase to the elongation factor 1 alpha","volume":"269","author":"VS Reed","year":"1994","journal-title":"J Biol Chem"},{"issue":"11","key":"ppat.1013057.ref053","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1016\/S1357-2725(03)00070-0","article-title":"Structure of the N-terminal extension of human aspartyl-tRNA synthetase: implications for its biological function","volume":"35","author":"H-K Cheong","year":"2003","journal-title":"Int J Biochem Cell Biol"},{"issue":"5","key":"ppat.1013057.ref054","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1006\/jmbi.2000.3791","article-title":"The free yeast aspartyl-tRNA synthetase differs from the tRNA(Asp)-complexed enzyme by structural changes in the catalytic site, hinge region, and anticodon-binding domain","volume":"299","author":"C Sauter","year":"2000","journal-title":"J Mol Biol"},{"issue":"9","key":"ppat.1013057.ref055","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.1016\/S0021-9258(17)37467-7","article-title":"Photoaffinity labeling of chloroquine-binding proteins in Plasmodium falciparum","volume":"269","author":"M Foley","year":"1994","journal-title":"J Biol Chem"},{"key":"ppat.1013057.ref056","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-1-4939-2074-7_5","article-title":"Culture and functional characterization of human hepatoma HepG2 cells","volume":"1250","author":"MT Donato","year":"2015","journal-title":"Methods Mol Biol"},{"issue":"6220","key":"ppat.1013057.ref057","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1126\/science.1260867","article-title":"Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates","volume":"347","author":"J Straimer","year":"2015","journal-title":"Science"},{"issue":"3","key":"ppat.1013057.ref058","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/S0006-3495(00)76713-0","article-title":"Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and lamm equation modeling","volume":"78","author":"P Schuck","year":"2000","journal-title":"Biophys J"},{"issue":"6","key":"ppat.1013057.ref059","article-title":"Purification of RNA using TRIzol (TRI reagent)","volume":"2010","author":"DC Rio","year":"2010","journal-title":"Cold Spring Harb Protoc"},{"key":"ppat.1013057.ref060","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1107\/S2053230X1500967X","article-title":"The MORPHEUS II protein crystallization screen","volume":"71","author":"F Gorrec","year":"2015","journal-title":"Acta Crystallogr F Struct Biol Commun"},{"key":"ppat.1013057.ref061","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1107\/S1600577518003120","article-title":"MX2: a high-flux undulator microfocus beamline serving both the chemical and macromolecular crystallography communities at the Australian Synchrotron","volume":"25","author":"D Arag\u00e3o","year":"2018","journal-title":"J Synchrotron Radiat"},{"key":"ppat.1013057.ref062","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1107\/S0907444909047337","article-title":"XDS","volume":"66","author":"W Kabsch","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ppat.1013057.ref063","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1107\/S0907444913000061","article-title":"How good are my data and what is the resolution?","volume":"69","author":"PR Evans","year":"2013","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ppat.1013057.ref064","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1107\/S2059798317017235","article-title":"DIALS: implementation and evaluation of a new integration package","volume":"74","author":"G Winter","year":"2018","journal-title":"Acta Crystallogr D Struct Biol"},{"key":"ppat.1013057.ref065","first-page":"293","article-title":"Data processing and analysis with the autoPROC toolbox","volume-title":"Acta Crystallogr D Biol Crystallogr","author":"C Vonrhein","year":"2011"},{"key":"ppat.1013057.ref066","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1107\/S0021889807021206","article-title":"Phaser crystallographic software","volume":"40","author":"AJ McCoy","year":"2007","journal-title":"J Appl Crystallogr"},{"key":"ppat.1013057.ref067","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1107\/S0907444905001307","article-title":"Auto-rickshaw: an automated crystal structure determination platform as an efficient tool for the validation of an X-ray diffraction experiment","volume":"61","author":"S Panjikar","year":"2005","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"4","key":"ppat.1013057.ref068","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1107\/S0907444912001308","article-title":"Towards automated crystallographic structure refinement with phenix.refine","volume":"68","author":"PV Afonine","year":"2012","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ppat.1013057.ref069","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":"ppat.1013057.ref070","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":"ppat.1013057.ref071","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1107\/S0907444909029436","article-title":"electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation","volume":"65","author":"NW Moriarty","year":"2009","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ppat.1013057.ref072","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1107\/S0907444909042073","article-title":"MolProbity: all-atom structure validation for macromolecular crystallography","volume":"66","author":"VB Chen","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"1","key":"ppat.1013057.ref073","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: More and better reference data for improved all-atom structure validation","volume":"27","author":"CJ Williams","year":"2018","journal-title":"Protein Sci"},{"issue":"13","key":"ppat.1013057.ref074","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualization system for exploratory research and analysis","volume":"25","author":"EF Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"ppat.1013057.ref075","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1107\/S2059798317001061","article-title":"CheckMyMetal: a macromolecular metal-binding validation tool","volume":"73","author":"H Zheng","year":"2017","journal-title":"Acta Crystallogr D Struct Biol"},{"issue":"10","key":"ppat.1013057.ref076","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: multiple ligand-protein interaction diagrams for drug discovery","volume":"51","author":"RA Laskowski","year":"2011","journal-title":"J Chem Inf Model"},{"key":"ppat.1013057.ref077","volume-title":"The PyMOL Molecular Graphics System, Version 2.5.4","author":"L Schr\u00f6dinger"},{"issue":"11","key":"ppat.1013057.ref078","article-title":"UCSF ChimeraX: Tools for structure building and analysis","volume":"32","author":"EC Meng","year":"2023","journal-title":"Protein Sci"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013057","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000}}],"container-title":["PLOS 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