{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T13:45:20Z","timestamp":1793454320923,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union's Horizon 2020 research and innovation programme","award":["101020135"],"award-info":[{"award-number":["101020135"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>The FoldX force field was originally validated with a database of 1000 mutants at a time when there were few high-resolution structures. Here, we have manually curated a database of 5556 mutants affecting protein stability, resulting in 2484 highly confident mutations denominated FoldX stability dataset (FSD), represented in non-redundant X-ray structures with &amp;lt;2.5\u2009\u00c5 resolution, not involving duplicates, metals, or prosthetic groups. Using this database, we have created a new version of the FoldX force field by introducing pi stacking, pH dependency for all charged residues, improving aromatic\u2013aromatic interactions, modifying the Ncap contribution and \u03b1-helix dipole, recalibrating the side-chain entropy of methionine, adjusting the H-bond parameters, and modifying the solvation contribution of tryptophan and others.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>These changes have led to significant improvements for the prediction of specific mutants involving the above residues\/interactions and a statistically significant increase of FoldX predictions, as well as for the majority of the 20 aa. Removing all training sets data from FSD [Validation FoldX Stability Dataset (VFSD) dataset] resulted in improved predictions from R\u2009=\u20090.693 (RMSE\u2009=\u20091.277\u2009kcal\/mol) to R\u2009=\u20090.706 (RMSE\u2009=\u20091.252\u2009kcal\/mol) when compared with the previously released version. FoldX achieves 95% accuracy considering an error of \u00b10.85\u2009kcal\/mol in prediction and an area under the curve\u2009=\u20090.78 for the VFSD, predicting the sign of the energy change upon mutation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>FoldX versions 4.1 and 5.1 are freely available for academics at https:\/\/foldxsuite.crg.eu\/.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf064","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T13:23:46Z","timestamp":1738848226000},"source":"Crossref","is-referenced-by-count":92,"title":["FoldX force field revisited, an improved version"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1302-5445","authenticated-orcid":false,"given":"Javier","family":"Delgado","sequence":"first","affiliation":[{"name":"The Barcelona Institute for Science and Technology Centre for Genomic Regulation (CRG), , Dr. Aiguader 88, Barcelona 08003,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Reche","sequence":"additional","affiliation":[{"name":"The Barcelona Institute for Science and Technology Centre for Genomic Regulation (CRG), , Dr. Aiguader 88, Barcelona 08003,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano","family":"Cianferoni","sequence":"additional","affiliation":[{"name":"The Barcelona Institute for Science and Technology Centre for Genomic Regulation (CRG), , Dr. Aiguader 88, Barcelona 08003,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5935-5258","authenticated-orcid":false,"given":"Gabriele","family":"Orlando","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, VIB , 3000 Leuven,","place":["Belgium"]},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven , 3000 Leuven,","place":["Belgium"]},{"name":"Switch Laboratory, VIB Center for AI & Computational Biology, VIB , 3000 Leuven,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"van der Kant","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, VIB , 3000 Leuven,","place":["Belgium"]},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven , 3000 Leuven,","place":["Belgium"]},{"name":"Switch Laboratory, VIB Center for AI & Computational Biology, VIB , 3000 Leuven,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-7399","authenticated-orcid":false,"given":"Frederic","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, VIB , 3000 Leuven,","place":["Belgium"]},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven , 3000 Leuven,","place":["Belgium"]},{"name":"Switch Laboratory, VIB Center for AI & Computational Biology, VIB , 3000 Leuven,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Schymkowitz","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, VIB , 3000 Leuven,","place":["Belgium"]},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven , 3000 Leuven,","place":["Belgium"]},{"name":"Switch Laboratory, VIB Center for AI & Computational Biology, VIB , 3000 Leuven,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5276-1392","authenticated-orcid":false,"given":"Luis","family":"Serrano","sequence":"additional","affiliation":[{"name":"The Barcelona Institute for Science and Technology Centre for Genomic Regulation (CRG), , Dr. Aiguader 88, Barcelona 08003,","place":["Spain"]},{"name":"Universitat Pompeu Fabra (UPF) , Barcelona 08002,","place":["Spain"]},{"name":"ICREA , Pg. 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