{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:39:12Z","timestamp":1793932752048,"version":"4.8.0"},"reference-count":97,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,3]],"date-time":"2024-11-03T00:00:00Z","timestamp":1730592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,11,3]],"date-time":"2024-11-03T00:00:00Z","timestamp":1730592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-024-53120-9","type":"journal-article","created":{"date-parts":[[2024,11,3]],"date-time":"2024-11-03T07:02:14Z","timestamp":1730617334000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4301-6382","authenticated-orcid":false,"given":"Rory","family":"Henderson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara","family":"Anasti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kartik","family":"Manne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1878-0581","authenticated-orcid":false,"given":"Victoria","family":"Stalls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1484-0396","authenticated-orcid":false,"given":"Carrie","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9131-005X","authenticated-orcid":false,"given":"Yishak","family":"Bililign","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashliegh","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pimthada","family":"Bubphamala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Montani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangita","family":"Kachhap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuancang","family":"Jaing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek W.","family":"Cain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sravani","family":"Venkatayogi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7552-6582","authenticated-orcid":false,"given":"Kshitij","family":"Wagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2026-5757","authenticated-orcid":false,"given":"Bette","family":"Korber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-7954","authenticated-orcid":false,"given":"Kevin O.","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-1271","authenticated-orcid":false,"given":"Fred","family":"Alt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Wiehe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0089-277X","authenticated-orcid":false,"given":"Priyamvada","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Munir","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7643-9023","authenticated-orcid":false,"given":"Barton F.","family":"Haynes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,3]]},"reference":[{"key":"53120_CR1","doi-asserted-by":"crossref","unstructured":"Haynes, B. F. et al. Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies. Nat. Rev. Immunol. 23, 142\u2013158 (2023).","DOI":"10.1038\/s41577-022-00753-w"},{"key":"53120_CR2","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/nbt.2197","volume":"30","author":"BF Haynes","year":"2012","unstructured":"Haynes, B. F., Kelsoe, G., Harrison, S. C. & Kepler, T. B. B-cell\u2013lineage immunogen design in vaccine development with HIV-1 as a case study. Nat. Biotechnol. 30, 423\u2013433 (2012).","journal-title":"Nat. Biotechnol."},{"key":"53120_CR3","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.chom.2018.04.018","volume":"23","author":"K Wiehe","year":"2018","unstructured":"Wiehe, K. et al. Functional relevance of improbable antibody mutations for HIV broadly neutralizing antibody development. Cell Host Microbe 23, 759\u2013765.e756 (2018).","journal-title":"Cell Host Microbe"},{"key":"53120_CR4","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1111\/imr.12508","volume":"275","author":"G Kelsoe","year":"2017","unstructured":"Kelsoe, G. & Haynes, B. F. Host controls of HIV broadly neutralizing antibody development. Immunol. Rev. 275, 79\u201388 (2017).","journal-title":"Immunol. Rev."},{"key":"53120_CR5","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.chom.2024.04.006","volume":"32","author":"K Wiehe","year":"2024","unstructured":"Wiehe, K. et al. Mutation-guided vaccine design: a process for developing boosting immunogens for HIV broadly neutralizing antibody induction. Cell Host Microbe 32, 693\u2013709.e697 (2024).","journal-title":"Cell Host Microbe"},{"key":"53120_CR6","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1016\/j.cell.2016.07.029","volume":"166","author":"M Tian","year":"2016","unstructured":"Tian, M. et al. Induction of HIV neutralizing antibody lineages in mice with diverse precursor repertoires. Cell 166, 1471\u20131484.e1418 (2016).","journal-title":"Cell"},{"key":"53120_CR7","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/imr.12505","volume":"275","author":"L Verkoczy","year":"2017","unstructured":"Verkoczy, L., Alt, F. W. & Tian, M. Human Ig knockin mice to study the development and regulation of HIV-1 broadly neutralizing antibodies. Immunol. Rev. 275, 89\u2013107 (2017).","journal-title":"Immunol. Rev."},{"key":"53120_CR8","doi-asserted-by":"publisher","first-page":"eaay7199","DOI":"10.1126\/science.aay7199","volume":"366","author":"KO Saunders","year":"2019","unstructured":"Saunders, K. O. et al. Targeted selection of HIV-specific antibody mutations by engineering B cell maturation. Science 366, eaay7199 (2019).","journal-title":"Science"},{"key":"53120_CR9","doi-asserted-by":"crossref","unstructured":"Sprumont, A., Rodrigues, A., McGowan, S. J., Bannard, C. & Bannard, O. Germinal centers output clonally diverse plasma cell populations expressing high- and low-affinity antibodies. Cell 186, 5486\u20135499 (2023).","DOI":"10.1016\/j.cell.2023.10.022"},{"key":"53120_CR10","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1146\/annurev-immunol-120419-022408","volume":"40","author":"GD Victora","year":"2022","unstructured":"Victora, G. D. & Nussenzweig, M. C. Germinal centers. Annu. Rev. Immunol. 40, 413\u2013442 (2022).","journal-title":"Annu. Rev. Immunol."},{"key":"53120_CR11","doi-asserted-by":"publisher","first-page":"7314","DOI":"10.4049\/jimmunol.0902452","volume":"183","author":"SM Anderson","year":"2009","unstructured":"Anderson, S. M. et al. Taking advantage: high-affinity B cells in the germinal center have lower death rates, but similar rates of division, compared to low-affinity cells. J. Immunol. 183, 7314\u20137325 (2009).","journal-title":"J. Immunol."},{"key":"53120_CR12","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1126\/science.1234150","volume":"340","author":"J Jardine","year":"2013","unstructured":"Jardine, J. et al. Rational HIV immunogen design to target specific germline B cell receptors. Science 340, 711 (2013).","journal-title":"Science"},{"key":"53120_CR13","unstructured":"Steichen, J. M. et al. A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses. Science 366, eaax4380 (2019)."},{"key":"53120_CR14","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/nsmb.2594","volume":"20","author":"L Kong","year":"2013","unstructured":"Kong, L. et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat. Struct. Mol. Biol. 20, 796\u2013803 (2013).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"53120_CR15","unstructured":"Bonsignori, M. et al. Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Sci. Transl. Med. 9, eaai7514 (2017)."},{"key":"53120_CR16","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1126\/science.1213256","volume":"334","author":"R Pejchal","year":"2011","unstructured":"Pejchal, R. et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 334, 1097\u20131103 (2011).","journal-title":"Science"},{"key":"53120_CR17","doi-asserted-by":"publisher","first-page":"E3268","DOI":"10.1073\/pnas.1217207109","volume":"109","author":"H Mouquet","year":"2012","unstructured":"Mouquet, H. et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc. Natl. Acad. Sci. USA 109, E3268\u2013E3277 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"53120_CR18","doi-asserted-by":"publisher","first-page":"eaal2144","DOI":"10.1126\/scitranslmed.aal2144","volume":"9","author":"NT Freund","year":"2017","unstructured":"Freund, N. T. et al. Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller. Sci. Transl. Med. 9, eaal2144 (2017).","journal-title":"Sci. Transl. Med."},{"key":"53120_CR19","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.immuni.2016.06.026","volume":"45","author":"D Sok","year":"2016","unstructured":"Sok, D. et al. A prominent site of antibody vulnerability on HIV envelope incorporates a motif associated with CCR5 binding and its camouflaging glycans. Immunity 45, 31\u201345 (2016).","journal-title":"Immunity"},{"key":"53120_CR20","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.cell.2016.02.022","volume":"165","author":"M Bonsignori","year":"2016","unstructured":"Bonsignori, M. et al. Maturation pathway from germline to broad HIV-1 neutralizer of a CD4-mimic antibody. Cell 165, 449\u2013463 (2016).","journal-title":"Cell"},{"key":"53120_CR21","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1107\/S1399004715013917","volume":"71","author":"L Kong","year":"2015","unstructured":"Kong, L. et al. Complete epitopes for vaccine design derived from a crystal structure of the broadly neutralizing antibodies PGT128 and 8ANC195 in complex with an HIV-1 Env trimer. Acta Crystallogr. Sect. D 71, 2099\u20132108 (2015).","journal-title":"Acta Crystallogr. Sect. D"},{"key":"53120_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12040","volume":"7","author":"L Kong","year":"2016","unstructured":"Kong, L. et al. Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability. Nat. Commun. 7, 12040 (2016).","journal-title":"Nat. Commun."},{"key":"53120_CR23","doi-asserted-by":"publisher","first-page":"eaba0468","DOI":"10.1126\/sciadv.aba0468","volume":"6","author":"RL Stanfield","year":"2020","unstructured":"Stanfield, R. L. et al. Structural basis of broad HIV neutralization by a vaccine-induced cow antibody. Sci. Adv. 6, eaba0468 (2020).","journal-title":"Sci. Adv."},{"key":"53120_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01640-y","volume":"8","author":"R Pantophlet","year":"2017","unstructured":"Pantophlet, R. et al. Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity. Nat. Commun. 8, 1601 (2017).","journal-title":"Nat. Commun."},{"key":"53120_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03565-6","volume":"9","author":"D Fera","year":"2018","unstructured":"Fera, D. et al. HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope. Nat. Commun. 9, 1111 (2018).","journal-title":"Nat. Commun."},{"key":"53120_CR26","doi-asserted-by":"publisher","first-page":"109561","DOI":"10.1016\/j.celrep.2021.109561","volume":"36","author":"O Swanson","year":"2021","unstructured":"Swanson, O. et al. Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations. Cell Rep. 36, 109561 (2021).","journal-title":"Cell Rep."},{"key":"53120_CR27","doi-asserted-by":"publisher","first-page":"4244","DOI":"10.1073\/pnas.1815431116","volume":"116","author":"AC Pan","year":"2019","unstructured":"Pan, A. C. et al. Atomic-level characterization of protein\u2013protein association. Proc. Natl. Acad. Sci. USA 116, 4244 (2019).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"53120_CR28","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1021\/ct400919u","volume":"10","author":"S Doerr","year":"2014","unstructured":"Doerr, S. & De Fabritiis, G. On-the-fly learning and sampling of ligand binding by high-throughput molecular simulations. J. Chem. Theory Comput. 10, 2064\u20132069 (2014).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR29","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.chom.2018.12.001","volume":"25","author":"CA Bricault","year":"2019","unstructured":"Bricault, C. A. et al. HIV-1 neutralizing antibody signatures and application to epitope-targeted vaccine design. Cell Host Microbe 25, 59\u201372.e58 (2019).","journal-title":"Cell Host Microbe"},{"key":"53120_CR30","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1038\/s41591-021-01509-0","volume":"27","author":"KE Stephenson","year":"2021","unstructured":"Stephenson, K. E. et al. Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial. Nat. Med. 27, 1718\u20131724 (2021).","journal-title":"Nat. Med."},{"key":"53120_CR31","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nm.4268","volume":"23","author":"M Caskey","year":"2017","unstructured":"Caskey, M. et al. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. Nat. Med. 23, 185\u2013191 (2017).","journal-title":"Nat. Med."},{"key":"53120_CR32","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1137\/070699500","volume":"7","author":"P Metzner","year":"2009","unstructured":"Metzner, P., Sch\u00fctte, C. & Vanden-Eijnden, E. Transition path theory for Markov jump processes. Multiscale Model. Simul. 7, 1192\u20131219 (2009).","journal-title":"Multiscale Model. Simul."},{"key":"53120_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38108-1","volume":"14","author":"R Henderson","year":"2023","unstructured":"Henderson, R. et al. Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage. Nat. Commun. 14, 2782 (2023).","journal-title":"Nat. Commun."},{"key":"53120_CR34","doi-asserted-by":"publisher","first-page":"R121","DOI":"10.1016\/S1359-0278(96)00056-9","volume":"1","author":"A Horovitz","year":"1996","unstructured":"Horovitz, A. Double-mutant cycles: a powerful tool for analyzing protein structure and function. Fold. Des. 1, R121\u2013R126 (1996).","journal-title":"Fold. Des."},{"key":"53120_CR35","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.jmb.2007.05.032","volume":"371","author":"M Harel","year":"2007","unstructured":"Harel, M., Cohen, M. & Schreiber, G. On the dynamic nature of the transition state for protein\u2013protein association as determined by double-mutant cycle analysis and simulation. J. Mol. Biol. 371, 180\u2013196 (2007).","journal-title":"J. Mol. Biol."},{"key":"53120_CR36","doi-asserted-by":"publisher","first-page":"111021","DOI":"10.1016\/j.celrep.2022.111021","volume":"39","author":"MA Hossain","year":"2022","unstructured":"Hossain, M. A. et al. B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates. Cell Rep. 39, 111021 (2022).","journal-title":"Cell Rep."},{"key":"53120_CR37","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1016\/j.cell.2015.05.007","volume":"161","author":"T Zhou","year":"2015","unstructured":"Zhou, T. et al. Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors. Cell 161, 1280\u20131292 (2015).","journal-title":"Cell"},{"key":"53120_CR38","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.immuni.2013.04.012","volume":"39","author":"T Zhou","year":"2013","unstructured":"Zhou, T. et al. Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity 39, 245\u2013258 (2013).","journal-title":"Immunity"},{"key":"53120_CR39","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1126\/science.1192819","volume":"329","author":"T Zhou","year":"2010","unstructured":"Zhou, T. et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329, 811 (2010).","journal-title":"Science"},{"key":"53120_CR40","doi-asserted-by":"publisher","first-page":"e1008026","DOI":"10.1371\/journal.ppat.1008026","volume":"15","author":"CC LaBranche","year":"2019","unstructured":"LaBranche, C. C. et al. Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. PLoS Pathog. 15, e1008026 (2019).","journal-title":"PLoS Pathog."},{"key":"53120_CR41","doi-asserted-by":"crossref","unstructured":"Saunders, K. O. et al. Vaccine induction of CD4-mimicking broadly neutralizing antibody precursors in macaques. Cell, 187, 79\u201394.e24 (2024).","DOI":"10.1016\/j.cell.2023.12.002"},{"key":"53120_CR42","doi-asserted-by":"publisher","first-page":"e1004932","DOI":"10.1371\/journal.ppat.1004932","volume":"11","author":"ET Crooks","year":"2015","unstructured":"Crooks, E. T. et al. Vaccine-elicited tier 2 HIV-1 neutralizing antibodies bind to quaternary epitopes involving glycan-deficient patches proximal to the CD4 binding site. PLoS Pathog. 11, e1004932 (2015).","journal-title":"PLoS Pathog."},{"key":"53120_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14196-w","volume":"11","author":"R Henderson","year":"2020","unstructured":"Henderson, R. et al. Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements. Nat. Commun. 11, 520 (2020).","journal-title":"Nat. Commun."},{"key":"53120_CR44","doi-asserted-by":"publisher","first-page":"e0167322","DOI":"10.1128\/jvi.01673-22","volume":"97","author":"D Wrapp","year":"2023","unstructured":"Wrapp, D. et al. Structure-based stabilization of SOSIP Env enhances recombinant ectodomain durability and Yield. J. Virol. 97, e0167322 (2023).","journal-title":"J. Virol."},{"key":"53120_CR45","doi-asserted-by":"publisher","first-page":"R155","DOI":"10.1016\/S0969-2126(99)80095-1","volume":"7","author":"MR Wormald","year":"1999","unstructured":"Wormald, M. R. & Dwek, R. A. Glycoproteins: glycan presentation and protein-fold stability. Structure 7, R155\u2013R160 (1999).","journal-title":"Structure"},{"key":"53120_CR46","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s00005-010-0072-3","volume":"58","author":"M Raska","year":"2010","unstructured":"Raska, M. & Novak, J. Involvement of envelope-glycoprotein glycans in HIV-1 biology and infection. Arch. Immunol. Ther. Exp. (Warsz.) 58, 191\u2013208 (2010).","journal-title":"Arch. Immunol. Ther. Exp. (Warsz.)"},{"key":"53120_CR47","doi-asserted-by":"publisher","first-page":"5663","DOI":"10.1073\/pnas.1112391109","volume":"109","author":"YD Kwon","year":"2012","unstructured":"Kwon, Y. D. et al. Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops. Proc. Natl. Acad. Sci. USA 109, 5663\u20135668 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"53120_CR48","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1021\/cr800373w","volume":"109","author":"G Schreiber","year":"2009","unstructured":"Schreiber, G., Haran, G. & Zhou, H. X. Fundamental aspects of protein\u2212protein association kinetics. Chem. Rev. 109, 839\u2013860 (2009).","journal-title":"Chem. Rev."},{"key":"53120_CR49","doi-asserted-by":"crossref","unstructured":"Shrock, E. L. et al. Germline-encoded amino acid\u2013binding motifs drive immunodominant public antibody responses. Science 380, eadc9498 (2023).","DOI":"10.1126\/science.adc9498"},{"key":"53120_CR50","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1002\/pro.4205","volume":"31","author":"TH Olsen","year":"2022","unstructured":"Olsen, T. H., Boyles, F. & Deane, C. M. Observed Antibody Space: a diverse database of cleaned, annotated, and translated unpaired and paired antibody sequences. Protein Sci. 31, 141\u2013146 (2022).","journal-title":"Protein Sci."},{"key":"53120_CR51","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/s41586-022-05371-z","volume":"611","author":"DB Jaffe","year":"2022","unstructured":"Jaffe, D. B. et al. Functional antibodies exhibit light chain coherence. Nature 611, 352\u2013357 (2022).","journal-title":"Nature"},{"key":"53120_CR52","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.celrep.2018.09.087","volume":"25","author":"K Wagh","year":"2018","unstructured":"Wagh, K. et al. Completeness of HIV-1 envelope glycan shield at transmission determines neutralization breadth. Cell Rep. 25, 893\u2013908.e897 (2018).","journal-title":"Cell Rep."},{"key":"53120_CR53","doi-asserted-by":"publisher","first-page":"9224","DOI":"10.1128\/JVI.01116-16","volume":"90","author":"Y Liang","year":"2016","unstructured":"Liang, Y. et al. Changes in structure and antigenicity of HIV-1 Env trimers resulting from removal of a conserved CD4 binding site-proximal glycan. J. Virol. 90, 9224 (2016).","journal-title":"J. Virol."},{"key":"53120_CR54","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1084\/jem.20122824","volume":"210","author":"AT McGuire","year":"2013","unstructured":"McGuire, A. T. et al. Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies. J. Exp. Med. 210, 655\u2013663 (2013).","journal-title":"J. Exp. Med."},{"key":"53120_CR55","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1016\/j.celrep.2019.10.071","volume":"29","author":"KR Parks","year":"2019","unstructured":"Parks, K. R. et al. Overcoming steric restrictions of VRC01 HIV-1 neutralizing antibodies through immunization. Cell Rep. 29, 3060\u20133072.e3067 (2019).","journal-title":"Cell Rep."},{"key":"53120_CR56","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.celrep.2017.04.013","volume":"19","author":"T Zhou","year":"2017","unstructured":"Zhou, T. et al. Quantification of the impact of the HIV-1-glycan shield on antibody elicitation. Cell Rep. 19, 719\u2013732 (2017).","journal-title":"Cell Rep."},{"key":"53120_CR57","doi-asserted-by":"publisher","first-page":"e1006614","DOI":"10.1371\/journal.ppat.1006614","volume":"13","author":"V Dubrovskaya","year":"2017","unstructured":"Dubrovskaya, V. et al. Targeted N-glycan deletion at the receptor-binding site retains HIV Env NFL trimer integrity and accelerates the elicited antibody response. PLoS Pathog. 13, e1006614\u2013e1006614 (2017).","journal-title":"PLoS Pathog."},{"key":"53120_CR58","doi-asserted-by":"publisher","first-page":"e1005815","DOI":"10.1371\/journal.ppat.1005815","volume":"12","author":"JG Jardine","year":"2016","unstructured":"Jardine, J. G. et al. Minimally mutated HIV-1 broadly neutralizing antibodies to guide reductionist vaccine design. PLoS Pathog. 12, e1005815 (2016).","journal-title":"PLoS Pathog."},{"key":"53120_CR59","doi-asserted-by":"publisher","first-page":"e1011401","DOI":"10.1371\/journal.ppat.1011401","volume":"19","author":"O Swanson","year":"2023","unstructured":"Swanson, O. et al. Identification of CDRH3 loops in the B cell receptor repertoire that can be engaged by candidate immunogens. PLoS Pathog. 19, e1011401 (2023).","journal-title":"PLoS Pathog."},{"key":"53120_CR60","doi-asserted-by":"publisher","first-page":"7938","DOI":"10.1021\/acs.jctc.1c00770","volume":"17","author":"S-H Ahn","year":"2021","unstructured":"Ahn, S.-H., Ojha, A. A., Amaro, R. E. & McCammon, J. A. Gaussian-accelerated molecular dynamics with the weighted ensemble method: a hybrid method improves thermodynamic and kinetic sampling. J. Chem. Theory Comput. 17, 7938\u20137951 (2021).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR61","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1021\/acs.jctc.3c01057","volume":"20","author":"S Mansoor","year":"2024","unstructured":"Mansoor, S., Baek, M., Park, H., Lee, G. R. & Baker, D. Protein ensemble generation through variational autoencoder latent space sampling. J. Chem. Theory Comput. 20, 2689\u20132695 (2024).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR62","doi-asserted-by":"crossref","unstructured":"Tian, H. et al. Explore protein conformational space with variational autoencoder. Front. Mol. Biosci. 8, 781635 (2021).","DOI":"10.3389\/fmolb.2021.781635"},{"key":"53120_CR63","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36443-x","volume":"14","author":"G Janson","year":"2023","unstructured":"Janson, G., Valdes-Garcia, G., Heo, L. & Feig, M. Direct generation of protein conformational ensembles via machine learning. Nat. Commun. 14, 774 (2023).","journal-title":"Nat. Commun."},{"key":"53120_CR64","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/nsmb.3051","volume":"22","author":"YD Kwon","year":"2015","unstructured":"Kwon, Y. D. et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat. Struct. Mol. Biol. 22, 522 (2015).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"53120_CR65","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1016\/j.cell.2015.11.056","volume":"163","author":"SW de Taeye","year":"2015","unstructured":"de Taeye, S. W. et al. Immunogenicity of stabilized HIV-1 Envelope trimers with reduced exposure of non-neutralizing epitopes. Cell 163, 1702\u20131715 (2015).","journal-title":"Cell"},{"key":"53120_CR66","unstructured":"Eswar, N. et al. in Current Protocols in Protein Science (John Wiley & Sons, Inc., 2001)."},{"key":"53120_CR67","unstructured":"Schrodinger, L. The PyMOL molecular graphics system Version 1, 8 (2015)."},{"key":"53120_CR68","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1002\/jcc.20945","volume":"29","author":"S Jo","year":"2008","unstructured":"Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859\u20131865 (2008).","journal-title":"J. Comput. Chem."},{"key":"53120_CR69","doi-asserted-by":"publisher","first-page":"3135","DOI":"10.1002\/jcc.21886","volume":"32","author":"S Jo","year":"2011","unstructured":"Jo, S., Song, K. C., Desaire, H., MacKerell, A. D. Jr & Im, W. Glycan Reader: automated sugar identification and simulation preparation for carbohydrates and glycoproteins. J. Comput. Chem. 32, 3135\u20133141 (2011).","journal-title":"J. Comput. Chem."},{"key":"53120_CR70","doi-asserted-by":"publisher","first-page":"3051","DOI":"10.1093\/bioinformatics\/btx358","volume":"33","author":"SJ Park","year":"2017","unstructured":"Park, S. J. et al. Glycan Reader is improved to recognize most sugar types and chemical modifications in the Protein Data Bank. Bioinformatics 33, 3051\u20133057 (2017).","journal-title":"Bioinformatics"},{"key":"53120_CR71","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1093\/glycob\/cwz003","volume":"29","author":"SJ Park","year":"2019","unstructured":"Park, S. J. et al. CHARMM-GUI Glycan Modeler for modeling and simulation of carbohydrates and glycoconjugates. Glycobiology 29, 320\u2013331 (2019).","journal-title":"Glycobiology"},{"key":"53120_CR72","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1002\/jcc.21287","volume":"30","author":"BR Brooks","year":"2009","unstructured":"Brooks, B. R. et al. CHARMM: the biomolecular simulation program. J. Comput. Chem. 30, 1545\u20131614 (2009).","journal-title":"J. Comput. Chem."},{"key":"53120_CR73","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1021\/acs.jctc.5b00935","volume":"12","author":"J Lee","year":"2016","unstructured":"Lee, J. et al. CHARMM-GUI input generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM\/OpenMM simulations using the CHARMM36 additive force field. J. Chem. Theory Comput. 12, 405\u2013413 (2016).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR74","doi-asserted-by":"crossref","unstructured":"Zhang, M. et al. Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14, 1229\u20131246 (2004).","DOI":"10.1093\/glycob\/cwh106"},{"key":"53120_CR75","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1021\/ct200909j","volume":"8","author":"AW Gotz","year":"2012","unstructured":"Gotz, A. W. et al. Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. Generalized born. J. Chem. Theory Comput. 8, 1542\u20131555 (2012).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR76","doi-asserted-by":"publisher","first-page":"3878","DOI":"10.1021\/ct400314y","volume":"9","author":"R Salomon-Ferrer","year":"2013","unstructured":"Salomon-Ferrer, R., Gotz, A. W., Poole, D., Le Grand, S. & Walker, R. C. Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle mesh Ewald. J. Chem. Theory Comput. 9, 3878\u20133888 (2013).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR77","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.cpc.2012.09.022","volume":"184","author":"S Le Grand","year":"2013","unstructured":"Le Grand, S., Gotz, A. W. & Walker, R. C. SPFP: speed without compromise\u2014a mixed precision model for GPU accelerated molecular dynamics simulations. Comput. Phys. Commun. 184, 374\u2013380 (2013).","journal-title":"Comput. Phys. Commun."},{"key":"53120_CR78","doi-asserted-by":"publisher","first-page":"3257","DOI":"10.1021\/ct300400x","volume":"8","author":"RB Best","year":"2012","unstructured":"Best, R. B. et al. Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone phi, psi and side-chain chi(1) and chi(2) dihedral angles. J. Chem. Theory Comput. 8, 3257\u20133273 (2012).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR79","doi-asserted-by":"publisher","first-page":"3162","DOI":"10.1021\/ct200328p","volume":"7","author":"O Guvench","year":"2011","unstructured":"Guvench, O. et al. CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate-protein modeling. J. Chem. Theory Comput. 7, 3162\u20133180 (2011).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR80","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1021\/ct200792v","volume":"8","author":"SS Mallajosyula","year":"2012","unstructured":"Mallajosyula, S. S., Guvench, O., Hatcher, E. & Mackerell, A. D.Jr. CHARMM additive all-atom force field for phosphate and sulfate linked to carbohydrates. J. Chem. Theory Comput. 8, 759\u2013776 (2012).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR81","doi-asserted-by":"publisher","first-page":"12981","DOI":"10.1021\/jp105758h","volume":"114","author":"EP Raman","year":"2010","unstructured":"Raman, E. P., Guvench, O. & MacKerell, A. D.Jr. CHARMM additive all-atom force field for glycosidic linkages in carbohydrates involving furanoses. J. Phys. Chem. B 114, 12981\u201312994 (2010).","journal-title":"J. Phys. Chem. B"},{"key":"53120_CR82","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","volume":"79","author":"WL Jorgensen","year":"1983","unstructured":"Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926\u2013935 (1983).","journal-title":"J. Chem. Phys."},{"key":"53120_CR83","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1063\/1.470117","volume":"103","author":"U Essmann","year":"1995","unstructured":"Essmann, U. et al. A smooth particle mesh Ewald method. J. Chem. Phys. 103, 8577\u20138593 (1995).","journal-title":"J. Chem. Phys."},{"key":"53120_CR84","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","volume":"23","author":"JP Ryckaert","year":"1977","unstructured":"Ryckaert, J. P., Ciccotti, G. & Berendsen, H. J. C. Numerical-integration of Cartesian equations of motion of a system with constraints\u2014molecular-dynamics of N-alkanes. J. Comput. Phys. 23, 327\u2013341 (1977).","journal-title":"J. Comput. Phys."},{"key":"53120_CR85","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1021\/ct5010406","volume":"11","author":"CW Hopkins","year":"2015","unstructured":"Hopkins, C. W., Le Grand, S., Walker, R. C. & Roitberg, A. E. Long-time-step molecular dynamics through hydrogen mass repartitioning. J. Chem. Theory Comput. 11, 1864\u20131874 (2015).","journal-title":"J. Chem. Theory Comput."},{"key":"53120_CR86","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/bip.360320508","volume":"32","author":"RJ Loncharich","year":"1992","unstructured":"Loncharich, R. J., Brooks, B. R. & Pastor, R. W. Langevin dynamics of peptides: the frictional dependence of isomerization rates of N-acetylalanyl-N\u2019-methylamide. Biopolymers 32, 523\u2013535 (1992).","journal-title":"Biopolymers"},{"key":"53120_CR87","unstructured":"Case, D. A. et al. Amber 2021 (University of California, 2021)."},{"key":"53120_CR88","doi-asserted-by":"crossref","unstructured":"Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat Methods. 14, 290\u2013296 (2017).","DOI":"10.1038\/nmeth.4169"},{"key":"53120_CR89","doi-asserted-by":"crossref","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol crystallogr 66, 486\u2013501 (2010).","DOI":"10.1107\/S0907444910007493"},{"key":"53120_CR90","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1107\/S2059798318006551","volume":"74","author":"PV Afonine","year":"2018","unstructured":"Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr D Struct. Biol. 74, 531\u2013544 (2018).","journal-title":"Acta Crystallogr D Struct. Biol."},{"key":"53120_CR91","doi-asserted-by":"crossref","unstructured":"Pettersen, E. F. et al. UCSF Chimera\u2013a visualization system for exploratory research and analysis. J Comput Chem. 25, 1605-1612 (2004).","DOI":"10.1002\/jcc.20084"},{"key":"53120_CR92","doi-asserted-by":"crossref","unstructured":"Meng, E. C. et al. UCSF ChimeraX: Tools for structure building and analysis. Protein Sci. 32, e4792 (2023).","DOI":"10.1002\/pro.4792"},{"key":"53120_CR93","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.jviromet.2009.02.014","volume":"158","author":"HX Liao","year":"2009","unstructured":"Liao, H. X. et al. High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies. J. Virol. Methods 158, 171\u2013179 (2009).","journal-title":"J. Virol. Methods"},{"key":"53120_CR94","doi-asserted-by":"publisher","first-page":"336ra362","DOI":"10.1126\/scitranslmed.aaf0618","volume":"8","author":"R Zhang","year":"2016","unstructured":"Zhang, R. et al. Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages. Sci. Transl. Med. 8, 336ra362 (2016).","journal-title":"Sci. Transl. Med."},{"key":"53120_CR95","doi-asserted-by":"publisher","first-page":"103","DOI":"10.12688\/f1000research.2-103.v1","volume":"2","author":"TB Kepler","year":"2013","unstructured":"Kepler, T. B. Reconstructing a B-cell clonal lineage. I. Statistical inference of unobserved ancestors. F1000Research 2, 103 (2013).","journal-title":"F1000Research"},{"key":"53120_CR96","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1016\/j.celrep.2017.02.003","volume":"18","author":"KO Saunders","year":"2017","unstructured":"Saunders, K. O. et al. Vaccine elicitation of high mannose-dependent neutralizing antibodies against the V3-glycan broadly neutralizing epitope in nonhuman primates. Cell Rep. 18, 2175\u20132188 (2017).","journal-title":"Cell Rep."},{"key":"53120_CR97","doi-asserted-by":"publisher","first-page":"10108","DOI":"10.1128\/JVI.79.16.10108-10125.2005","volume":"79","author":"M Li","year":"2005","unstructured":"Li, M. et al. Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol. 79, 10108\u201310125 (2005).","journal-title":"J. Virol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-53120-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-53120-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-53120-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T11:04:36Z","timestamp":1730891076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-53120-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,3]]},"references-count":97,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["53120"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-53120-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.12.15.571700","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,3]]},"assertion":[{"value":"31 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare the following competing interests: A patent covering HIV-1 Envelope modifications based on this study has been issued: Patent number US-20240197854-A1. The authors declare no other competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9503"}}