{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:03:10Z","timestamp":1776322990480,"version":"3.50.1"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100009559","name":"Universidad Nacional de Quilmes","doi-asserted-by":"publisher","award":["PUNQ 1309\/19"],"award-info":[{"award-number":["PUNQ 1309\/19"]}],"id":[{"id":"10.13039\/501100009559","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021778","name":"Agencia Nacional de Promoci\u00f3n de la Investigaci\u00f3n, el Desarrollo Tecnol\u00f3gico y la Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PICT-2018 3457"],"award-info":[{"award-number":["PICT-2018 3457"]}],"id":[{"id":"10.13039\/501100021778","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"crossref","award":["PIP-2015-2017 11220150100853CO"],"award-info":[{"award-number":["PIP-2015-2017 11220150100853CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Union's Horizon 2020 Research and Innovation Staff Exchange Program","award":["778247"],"award-info":[{"award-number":["778247"]}]},{"name":"European Union's Horizon 2020 Research and Innovation Staff Exchange Program","award":["823886"],"award-info":[{"award-number":["823886"]}]},{"DOI":"10.13039\/501100002923","name":"CONICET","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here, we address the performance of AlphaFold2 predictions obtained through ColabFold under this ensemble paradigm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Using a curated collection of apo\u2013holo pairs of conformers, we found that AlphaFold2 predicts the holo form of a protein in \u223c70% of the cases, being unable to reproduce the observed conformational diversity with the same error for both conformers. More importantly, we found that AlphaFold2's performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo\u2013holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>Data and code used in this manuscript are publicly available at https:\/\/gitlab.com\/sbgunq\/publications\/af2confdiv-oct2021.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  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Argentina"}]},{"given":"Ana Julia","family":"Velez Rueda","sequence":"additional","affiliation":[{"name":"Departamento de Ciencia y Tecnolog\u00eda, Universidad Nacional de Quilmes , Bernal, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas , Buenos Aires, Argentina"}]},{"given":"Eduardo","family":"Gonik","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas , Buenos Aires, Argentina"},{"name":"INIFTA (CONICET-UNLP) \u2013 Fotoqu\u00edmica y Nanomateriales para el Ambiente y la Biolog\u00eda (nanoFOT) , La Plata, Argentina"}]},{"given":"Agustina","family":"Garc\u00eda Melani","sequence":"additional","affiliation":[{"name":"IMBICE (CONICET \u2013 UNLP), Laboratorio de Electrofisiolog\u00eda , La Plata, Argentina"}]},{"given":"Julieta","family":"Novomisky Nechcoff","sequence":"additional","affiliation":[{"name":"Departamento de Ciencia y Tecnolog\u00eda, Universidad Nacional de Quilmes 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