{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:47:18Z","timestamp":1792165638050,"version":"4.4.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Awarding Institution: National Heart, Lung, and Blood Institute, National Institutes of Health","award":["5T32HL144446-04"],"award-info":[{"award-number":["5T32HL144446-04"]}]},{"name":"Awarding Institution: National Heart, Lung, and Blood Institute, National Institutes of Health","award":["5R35HL140016-05"],"award-info":[{"award-number":["5R35HL140016-05"]}]},{"name":"Awarding Institution: National Institute of Drug Abuse, National Institutes of Health","award":["5R01DA046138-03"],"award-info":[{"award-number":["5R01DA046138-03"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Computation methods that predict the binding of peptides to MHC-I are important tools for screening and identifying immunogenic antigens and have the potential to accelerate vaccine and drug development. However, most available tools are sequence-based and optimized only for peptides containing the twenty canonical amino acids. This omits a large number of peptides containing non-canonical amino acids (NCAA), or residues that undergo varied post-translational modifications such as glycosylation or phosphorylation. These modifications fundamentally alter peptide immunogenicity. Similarly, existing structure-based methods are biased towards canonical peptide backbone structures, which may or may not be preserved when NCAAs are present. Rosetta FlexPepDock\n                    <jats:italic>ab-initio<\/jats:italic>\n                    is a structure-based computational protocol able to evaluate peptide-receptor interaction where no prior information of the peptide backbone is known. We benchmarked FlexPepDock\n                    <jats:italic>ab-initio<\/jats:italic>\n                    for docking canonical peptides to MHC-I, and illustrate for the first time the method\u2019s ability to accurately model MHC-I bound epitopes containing NCAAs. FlexPepDock\n                    <jats:italic>ab-initio<\/jats:italic>\n                    protocol was able to recapitulate near-native structures (\u22641.5\u00c5) in the top lowest-energy models for 20 out of 25 cases in our initial benchmark. Using known experimental binding affinities of twenty peptides derived from an influenza-derived peptide, we showed that FlexPepDock protocol is able to predict relative binding affinity as Rosetta energies correlate well with experimental values (r = 0.59, p = 0.006). ROC analysis revealed 80% true positive and a 40% false positive rate, with a prediction power of 93%. Finally, we demonstrate the protocol\u2019s ability to accurately recapitulate HLA-A*02:01 bound phosphopeptide backbone structures and relative binding affinity changes, the theoretical structure of the lymphocytic choriomeningitis derived glycosylated peptide GP392 bound to MHC-I H-2D\n                    <jats:sup>b<\/jats:sup>\n                    , and isolevuglandin-adducted peptides. The ability to use non-canonical amino acids in the Rosetta FlexPepDock protocol may provide useful insight into critical amino acid positions where the post-translational modification modulates immunologic responses.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0275759","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T13:53:06Z","timestamp":1670939586000},"page":"e0275759","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Rosetta FlexPepDock to predict peptide-MHC binding: An approach for non-canonical amino acids"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-003X","authenticated-orcid":true,"given":"Nathaniel","family":"Bloodworth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia Ruggeri","family":"Barbaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Moretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8945-193X","authenticated-orcid":true,"given":"Jens","family":"Meiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"pone.0275759.ref001","first-page":"6","article-title":"Intracellular Transport Routes for MHC I and Their Relevance for Antigen Cross-Presentation","author":"AC Adiko","year":"2015","journal-title":"Front 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