{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:21:30Z","timestamp":1772173290368,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011519","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010722","name":"Harbin Medical University","doi-asserted-by":"publisher","award":["310212000109"],"award-info":[{"award-number":["310212000109"]}],"id":[{"id":"10.13039\/100010722","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010722","name":"Harbin Medical University","doi-asserted-by":"publisher","award":["31011210004"],"award-info":[{"award-number":["31011210004"]}],"id":[{"id":"10.13039\/100010722","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Provincial Basic Research Fund for Universities","award":["2023-KYYWF-0265"],"award-info":[{"award-number":["2023-KYYWF-0265"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22002096"],"award-info":[{"award-number":["22002096"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    ASPP2 and iASPP bind to p53 through their conserved ANK-SH3 domains to respectively promote and inhibit p53-dependent cell apoptosis. While crystallography has indicated that these two proteins employ distinct surfaces of their ANK-SH3 domains to bind to p53, solution NMR data has suggested similar surfaces. In this study, we employed multi-scale molecular dynamics (MD) simulations combined with free energy calculations to reconcile the discrepancy in the binding modes. We demonstrated that the binding mode based solely on a single crystal structure does not enable iASPP\u2019s RT loop to engage with p53\u2019s C-terminal linker\u2014a verified interaction. Instead, an ensemble of simulated iASPP-p53 complexes facilitates this interaction. We showed that the ensemble-average inter-protein contacting residues and NMR-detected interfacial residues qualitatively overlap on ASPP proteins, and the ensemble-average binding free energies better match experimental K\n                    <jats:sub>\n                      <jats:italic>D<\/jats:italic>\n                    <\/jats:sub>\n                    values compared to single crystallgarphy-determined binding mode. For iASPP, the sampled ensemble complexes can be grouped into two classes, resembling the binding modes determined by crystallography and solution NMR. We thus propose that crystal packing shifts the equilibrium of binding modes towards the crystallography-determined one. Lastly, we showed that the ensemble binding complexes are sensitive to p53\u2019s intrinsically disordered regions (IDRs), attesting to experimental observations that these IDRs contribute to biological functions. Our results provide a dynamic and ensemble perspective for scrutinizing these important cancer-related protein-protein interactions (PPIs).\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1011519","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T13:41:16Z","timestamp":1707313276000},"page":"e1011519","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reconciling ASPP-p53 binding mode discrepancies through an ensemble binding framework that bridges crystallography and NMR data"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3205-0988","authenticated-orcid":true,"given":"Te","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sichao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2583-4493","authenticated-orcid":true,"given":"Bin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"issue":"4","key":"pcbi.1011519.ref001","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S1097-2765(01)00367-7","article-title":"ASPP proteins specifically stimulate the apoptotic function of p53","volume":"8","author":"Y Samuels-Lev","year":"2001","journal-title":"Mol Cell"},{"issue":"4","key":"pcbi.1011519.ref002","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1093\/jmcb\/mjz009","article-title":"Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting","volume":"11","author":"YS Tan","year":"2019","journal-title":"J Mol Cell Biol"},{"issue":"10","key":"pcbi.1011519.ref003","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.str.2019.07.012","article-title":"Flexible Tethering of ASPP Proteins Facilitates PP-1c","volume":"27","author":"Y Zhou","year":"2019","journal-title":"Structure"},{"issue":"20","key":"pcbi.1011519.ref004","doi-asserted-by":"crossref","first-page":"13812","DOI":"10.1074\/jbc.M808821200","article-title":"Insight into the structural basis of pro- and antiapoptotic p53 modulation by ASPP proteins","volume":"284","author":"J Ahn","year":"2009","journal-title":"J Biol Chem"},{"issue":"5289","key":"pcbi.1011519.ref005","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1126\/science.274.5289.1001","article-title":"Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2","volume":"274","author":"S Gorina","year":"1996","journal-title":"Science"},{"issue":"35","key":"pcbi.1011519.ref006","doi-asserted-by":"crossref","first-page":"17470","DOI":"10.1073\/pnas.1909393116","article-title":"iASPP mediates p53 selectivity through a modular mechanism fine-tuning DNA recognition","volume":"116","author":"Shuo Chen","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pcbi.1011519.ref007","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.str.2007.11.012","article-title":"Biochemical and structural studies of ASPP proteins reveal differential binding to p53, p63, and p73","volume":"16","author":"RA Robinson","year":"2008","journal-title":"Structure"},{"issue":"43","key":"pcbi.1011519.ref008","doi-asserted-by":"crossref","first-page":"32526","DOI":"10.1074\/jbc.M604725200","article-title":"Effects of oncogenic mutations and DNA response elements on the binding of p53 to p53-binding protein 2 (53BP2)","volume":"281","author":"H Tidow","year":"2006","journal-title":"J Biol Chem"},{"issue":"16","key":"pcbi.1011519.ref009","doi-asserted-by":"crossref","first-page":"5139","DOI":"10.1093\/nar\/gkn490","article-title":"Molecular interactions of ASPP1 and ASPP2 with the p53 protein family and the apoptotic promoters PUMA and Bax","volume":"36","author":"S Patel","year":"2008","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pcbi.1011519.ref010","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/jcc.21303","article-title":"Crystal contacts as nature\u2019s docking solutions","volume":"31","author":"E Krissinel","year":"2010","journal-title":"J Comput Chem"},{"key":"pcbi.1011519.ref011","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.bb.21.060192.001123","article-title":"NMR structure determination in solution: a critique and comparison with X-ray crystallography","volume":"21","author":"G Wagner","year":"1992","journal-title":"Annu Rev Biophys Biomol Struct"},{"issue":"1","key":"pcbi.1011519.ref012","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/pro.2774","article-title":"A community resource of experimental data for NMR \/ X-ray crystal structure pairs","volume":"25","author":"JK Everett","year":"2016","journal-title":"Protein Sci"},{"issue":"1","key":"pcbi.1011519.ref013","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/s41467-023-36734-3","article-title":"Robust total X-ray scattering workflow to study correlated motion of proteins in crystals","volume":"14","author":"SP Meisburger","year":"2023","journal-title":"Nat Commun"},{"issue":"5","key":"pcbi.1011519.ref014","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1021\/acs.accounts.9b00066","article-title":"What Your Crystal Structure Will Not Tell You about Enzyme Function","volume":"52","author":"TC Pochapsky","year":"2019","journal-title":"Acc Chem Res"},{"issue":"2","key":"pcbi.1011519.ref015","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1021\/acs.jcim.2c01280","article-title":"Predictions of the Poses and Affinity of a Ligand over the Entire Surface of a NEET Protein: The Case of Human MitoNEET","volume":"63","author":"K Zuo","year":"2023","journal-title":"J Chem Inf Model"},{"key":"pcbi.1011519.ref016","first-page":"3823","article-title":"AMBER2020, university of California, San Fransisco","volume":"142","author":"DA Case","year":"2020","journal-title":"J. Amer. Chem. Soc"},{"issue":"1","key":"pcbi.1011519.ref017","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1021\/acs.jctc.9b00591","article-title":"ff19SB: Amino-Acid-Specific Protein Backbone Parameters Trained against Quantum Mechanics Energy Surfaces in Solution","volume":"16","author":"C Tian","year":"2020","journal-title":"J Chem Theory Comput"},{"issue":"3","key":"pcbi.1011519.ref018","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes","volume":"23","author":"Jean-Paul Ryckaert","year":"1977","journal-title":"J Comput Phys"},{"issue":"23","key":"pcbi.1011519.ref019","doi-asserted-by":"crossref","first-page":"234101","DOI":"10.1063\/1.3149788","article-title":"Langevin thermostat for rigid body dynamics","volume":"130","author":"RL Davidchack","year":"2009","journal-title":"J Chem Phys"},{"issue":"12","key":"pcbi.1011519.ref020","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An Nlog(N) method for Ewald sums in large systems","volume":"98","author":"Tom Darden","year":"1993","journal-title":"J Chem Phys"},{"issue":"4","key":"pcbi.1011519.ref021","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1021\/ct5010406","article-title":"Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning","volume":"11","author":"CW Hopkins","year":"2015","journal-title":"J Chem Theory Comput"},{"issue":"24","key":"pcbi.1011519.ref022","doi-asserted-by":"crossref","first-page":"7483","DOI":"10.1021\/bi0603165","article-title":"Effect of Zn2+ on DNA recognition and stability of the p53 DNA-binding domain","volume":"45","author":"J Duan","year":"2006","journal-title":"Biochemistry"},{"issue":"8","key":"pcbi.1011519.ref023","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1021\/bi026635n","article-title":"Structure, function, and aggregation of the zinc-free form of the p53 DNA binding domain","volume":"42","author":"JS Butler","year":"2003","journal-title":"Biochemistry"},{"issue":"7","key":"pcbi.1011519.ref024","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1128\/MCB.15.7.3892","article-title":"Role of cysteine residues in regulation of p53 function","volume":"15","author":"R Rainwater","year":"1995","journal-title":"Mol Cell Biol"},{"issue":"6","key":"pcbi.1011519.ref025","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1021\/ct400146w","article-title":"Rational Design of Particle Mesh Ewald Compatible Lennard-Jones Parameters for +2 Metal Cations in Explicit Solvent","volume":"9","author":"P Li","year":"2013","journal-title":"J Chem Theory Comput"},{"issue":"4","key":"pcbi.1011519.ref026","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41592-021-01098-3","article-title":"Martini 3: a general purpose force field for coarse-grained molecular dynamics","volume":"18","author":"PCT Souza","year":"2021","journal-title":"Nat Methods"},{"key":"pcbi.1011519.ref027","unstructured":"Kroon Peter C, Gr\u00fcnewald Fabian, Barnoud Jonathan, van Tilburg Marco, Souza Paulo CT, Wassenaar Tsjerk A, Marrink Siewert-Jan Martinize2 and Vermouth: Unified Framework for Topology Generation arXiv preprint arXiv:2212.01191"},{"issue":"Database issue","key":"pcbi.1011519.ref028","doi-asserted-by":"crossref","first-page":"D364","DOI":"10.1093\/nar\/gku1028","article-title":"A series of PDB-related databanks for everyday needs","volume":"43","author":"WG Touw","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"pcbi.1011519.ref029","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1002\/bip.360221211","article-title":"Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features","volume":"22","author":"W Kabsch","year":"1983","journal-title":"Biopolymers"},{"issue":"12","key":"pcbi.1011519.ref030","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1016\/j.bbagen.2018.07.027","article-title":"Electrostatic control of calcineurin\u2019s intrinsically-disordered regulatory domain binding to calmodulin","volume":"1862","author":"B Sun","year":"2018","journal-title":"Biochim Biophys Acta Gen Subj"},{"issue":"6","key":"pcbi.1011519.ref031","doi-asserted-by":"crossref","first-page":"e1000810","DOI":"10.1371\/journal.pcbi.1000810","article-title":"Polarizable water model for the coarse-grained MARTINI force field","volume":"6","author":"SO Yesylevskyy","year":"2010","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1011519.ref032","unstructured":"Lindahl and Abraham and Hess and van der Spoel GROMACS 2020.4 Manual Zenodo. 2020 Oct"},{"issue":"2","key":"pcbi.1011519.ref033","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1021\/ct400617g","article-title":"Going Backward: A Flexible Geometric Approach to Reverse Transformation from Coarse Grained to Atomistic Models","volume":"10","author":"TA Wassenaar","year":"2014","journal-title":"J Chem Theory Comput"},{"key":"pcbi.1011519.ref034","unstructured":"Grossfield, Alan WHAM: the weighted histogram analysis method, version"},{"issue":"32","key":"pcbi.1011519.ref035","doi-asserted-by":"crossref","first-page":"13023","DOI":"10.1073\/pnas.1108486108","article-title":"From the Cover: Simplifying the representation of complex free-energy landscapes using sketch-map","volume":"108","author":"M Ceriotti","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"14","key":"pcbi.1011519.ref036","doi-asserted-by":"crossref","first-page":"5196","DOI":"10.1073\/pnas.1201152109","article-title":"Using sketch-map coordinates to analyze and bias molecular dynamics simulations","volume":"109","author":"GA Tribello","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pcbi.1011519.ref037","doi-asserted-by":"crossref","first-page":"20180062","DOI":"10.1098\/rsfs.2018.0062","article-title":"Simulating and analysing configurational landscapes of protein-protein contact formation","volume":"9","author":"A Berg","year":"2019","journal-title":"Interface Focus. Interface Focus"},{"issue":"7","key":"pcbi.1011519.ref038","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data","volume":"9","author":"DR Roe","year":"2013","journal-title":"J Chem Theory Comput"},{"issue":"8","key":"pcbi.1011519.ref039","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1016\/j.bpj.2015.08.015","article-title":"MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories","volume":"109","author":"RT McGibbon","year":"2015","journal-title":"Biophys J"},{"issue":"1","key":"pcbi.1011519.ref040","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/pro.3235","article-title":"UCSF ChimeraX: Meeting modern challenges in visualization and analysis","volume":"27","author":"TD Goddard","year":"2018","journal-title":"Protein Sci"},{"issue":"1","key":"pcbi.1011519.ref041","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"},{"issue":"1","key":"pcbi.1011519.ref042","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: visual molecular dynamics","volume":"14","author":"W Humphrey","year":"1996","journal-title":"J Mol Graph"},{"issue":"45","key":"pcbi.1011519.ref043","doi-asserted-by":"crossref","first-page":"10240","DOI":"10.1002\/chem.202000465","article-title":"Targeting an Interaction Between Two Disordered Domains by Using a Designed Peptide","volume":"26","author":"G Mayer","year":"2020","journal-title":"Chemistry"},{"issue":"9","key":"pcbi.1011519.ref044","doi-asserted-by":"crossref","first-page":"4990","DOI":"10.3390\/ijms22094990","article-title":"Assessing the Role of Calmodulin\u2019s Linker Flexibility in Target Binding","volume":"22","author":"B Sun","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"23","key":"pcbi.1011519.ref045","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.1002\/pmic.200900303","article-title":"The structural analysis of protein\u2013protein interactions by NMR spectroscopy","volume":"9","author":"MR O\u2019Connell","year":"2009","journal-title":"Proteomics"},{"issue":"8","key":"pcbi.1011519.ref046","doi-asserted-by":"crossref","first-page":"e0270572","DOI":"10.1371\/journal.pone.0270572","article-title":"Validation of the solution structure of dimerization domain of PRC1","volume":"17","author":"F Tan","year":"2022","journal-title":"PLoS One"},{"issue":"3","key":"pcbi.1011519.ref047","doi-asserted-by":"crossref","first-page":"e58470","DOI":"10.1371\/journal.pone.0058470","article-title":"Regulation of ASPP2 interaction with p53 core domain by an intramolecular autoinhibitory mechanism","volume":"8","author":"S Rotem-Bamberger","year":"2013","journal-title":"PLoS One"},{"key":"pcbi.1011519.ref048","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1017\/S003358352300001X","article-title":"Myofilament-associated proteins with intrinsic disorder (MAPIDs) and their resolution by computational modeling","volume":"56","author":"B Sun","year":"2023","journal-title":"Q Rev Biophys"},{"issue":"16","key":"pcbi.1011519.ref049","doi-asserted-by":"crossref","first-page":"8868","DOI":"10.1073\/pnas.160259697","article-title":"Speeding molecular recognition by using the folding funnel: the fly-casting mechanism","volume":"97","author":"BA Shoemaker","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pcbi.1011519.ref050","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1021\/cr800373w","article-title":"Fundamental Aspects of ProteinProtein Association Kinetics","volume":"109","author":"G Schreiber","year":"2009","journal-title":"Chemical Reviews"},{"key":"pcbi.1011519.ref051","doi-asserted-by":"crossref","first-page":"e01370","DOI":"10.7554\/eLife.01370","article-title":"Encounter complexes and dimensionality reduction in protein\u2013protein association","volume":"3","author":"D Kozakov","year":"2014","journal-title":"Elife"},{"issue":"8","key":"pcbi.1011519.ref052","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1039\/C8SC04811H","article-title":"Protein-protein binding pathways and calculations of rate constants using fully-continuous, explicit-solvent simulations","volume":"10","author":"AS Saglam","year":"2018","journal-title":"Chem Sci"},{"issue":"12","key":"pcbi.1011519.ref053","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/j.str.2004.09.014","article-title":"Complementarity of Structure Ensembles in Protein-Protein Binding","volume":"12","author":"R Gr\u00fcnberg","year":"2004","journal-title":"Structure"},{"issue":"3","key":"pcbi.1011519.ref054","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/S0006-3495(99)77281-4","article-title":"Free energy landscapes of encounter complexes in protein-protein association","volume":"76","author":"CJ Camacho","year":"1999","journal-title":"Biophys J"},{"issue":"4","key":"pcbi.1011519.ref055","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.bbrc.2016.12.027","article-title":"DeltaN-ASPP2, a novel isoform of the ASPP2 tumor suppressor, promotes cellular survival","volume":"482","author":"K Van Hook","year":"2017","journal-title":"Biochem Biophys Res Commun"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1011519","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011519","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T13:36:26Z","timestamp":1708436186000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011519"}},"subtitle":[],"editor":[{"given":"Vlad","family":"Cojocaru","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,7]]},"references-count":55,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1011519","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.09.17.558183","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,7]]}}}