{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T08:17:13Z","timestamp":1772525833767,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"S14","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T00:00:00Z","timestamp":1562112000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2019,7]]},"DOI":"10.1186\/s12859-019-2923-1","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T00:02:39Z","timestamp":1562112159000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":148,"title":["DDGun: an untrained method for the prediction of protein stability changes upon single and multiple point variations"],"prefix":"10.1186","volume":"20","author":[{"given":"Ludovica","family":"Montanucci","sequence":"first","affiliation":[]},{"given":"Emidio","family":"Capriotti","sequence":"additional","affiliation":[]},{"given":"Yotam","family":"Frank","sequence":"additional","affiliation":[]},{"given":"Nir","family":"Ben-Tal","sequence":"additional","affiliation":[]},{"given":"Piero","family":"Fariselli","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,7,3]]},"reference":[{"issue":"48","key":"2923_CR1","doi-asserted-by":"publisher","first-page":"8601","DOI":"10.1021\/bi4001529","volume":"52","author":"M Compiani","year":"2013","unstructured":"Compiani M, Capriotti E. Computational and theoretical methods for protein folding. Biochemistry. 2013;52(48):8601\u201324.","journal-title":"Biochemistry"},{"issue":"6","key":"2923_CR2","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/humu.21242","volume":"31","author":"S Khan","year":"2010","unstructured":"Khan S, Vihinen M. Performance of protein stability predictors. Hum Mutat. 2010;31(6):675\u201384.","journal-title":"Hum Mutat"},{"issue":"11","key":"2923_CR3","doi-asserted-by":"publisher","first-page":"2714","DOI":"10.1110\/ps.0217002","volume":"11","author":"H Zhou","year":"2002","unstructured":"Zhou H, Zhou Y. Distance-scaled, finite ideal-gas reference state improves structure-derived potentials of mean force for structure selection and stability prediction. Protein Sci. 2002;11(11):2714\u201326.","journal-title":"Protein Sci"},{"issue":"2","key":"2923_CR4","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/S0022-2836(02)00442-4","volume":"320","author":"R Guerois","year":"2002","unstructured":"Guerois R, Nielsen JE, Serrano L. Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. J Mol Biol. 2002;320(2):369\u201387.","journal-title":"J Mol Biol"},{"issue":"Suppl 1","key":"2923_CR5","doi-asserted-by":"publisher","first-page":"i63","DOI":"10.1093\/bioinformatics\/bth928","volume":"20","author":"E Capriotti","year":"2004","unstructured":"Capriotti E, Fariselli P, Casadio R. A neural-network-based method for predicting protein stability changes upon single point mutations. Bioinformatics. 2004;20(Suppl 1):i63\u20138.","journal-title":"Bioinformatics"},{"issue":"Web Server","key":"2923_CR6","doi-asserted-by":"publisher","first-page":"W306","DOI":"10.1093\/nar\/gki375","volume":"33","author":"E Capriotti","year":"2005","unstructured":"Capriotti E, Fariselli P, Casadio R. I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure. Nucleic Acids Res. 2005;33(Web Server):W306\u201310.","journal-title":"Nucleic Acids Res"},{"issue":"Web Server","key":"2923_CR7","doi-asserted-by":"publisher","first-page":"W239","DOI":"10.1093\/nar\/gkl190","volume":"34","author":"V Parthiban","year":"2006","unstructured":"Parthiban V, Gromiha MM, Schomburg D. CUPSAT: prediction of protein stability upon point mutations. Nucleic Acids Res. 2006;34(Web Server):W239\u201342.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"2923_CR8","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/nmeth0607-466","volume":"4","author":"S Yin","year":"2007","unstructured":"Yin S, Ding F, Dokholyan NV. Eris: an automated estimator of protein stability. Nat Methods. 2007;4(6):466\u20137.","journal-title":"Nat Methods"},{"issue":"18","key":"2923_CR9","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1093\/bioinformatics\/btn353","volume":"24","author":"M Masso","year":"2008","unstructured":"Masso M, Vaisman II. Accurate prediction of stability changes in protein mutants by combining machine learning with structure based computational mutagenesis. Bioinformatics. 2008;24(18):2002\u20139.","journal-title":"Bioinformatics"},{"issue":"Suppl 2","key":"2923_CR10","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1186\/1471-2105-9-S2-S6","volume":"9","author":"E Capriotti","year":"2008","unstructured":"Capriotti E, Fariselli P, Rossi I, Casadio R. A three-state prediction of single point mutations on protein stability changes. BMC bioinformatics. 2008;9(Suppl 2):S6.","journal-title":"BMC bioinformatics"},{"key":"2923_CR11","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/1471-2105-12-151","volume":"12","author":"Y Dehouck","year":"2011","unstructured":"Dehouck Y, Kwasigroch JM, Gilis D, Rooman M. PoPMuSiC 2.1: a web server for the estimation of protein stability changes upon mutation and sequence optimality. BMC bioinformatics. 2011;12:151.","journal-title":"BMC bioinformatics"},{"issue":"23","key":"2923_CR12","doi-asserted-by":"publisher","first-page":"3286","DOI":"10.1093\/bioinformatics\/btr576","volume":"27","author":"G Wainreb","year":"2011","unstructured":"Wainreb G, Wolf L, Ashkenazy H, Dehouck Y, Ben-Tal N. Protein stability: a single recorded mutation aids in predicting the effects of other mutations in the same amino acid site. Bioinformatics. 2011;27(23):3286\u201392.","journal-title":"Bioinformatics"},{"key":"2923_CR13","doi-asserted-by":"publisher","first-page":"W215","DOI":"10.1093\/nar\/gkr363","volume":"39","author":"CL Worth","year":"2011","unstructured":"Worth CL, Preissner R, Blundell TL. SDM--a server for predicting effects of mutations on protein stability and malfunction. Nucleic Acids Res. 2011;39(Web Server issue:W215\u201322.","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"2923_CR14","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1093\/bioinformatics\/btt691","volume":"30","author":"DE Pires","year":"2014","unstructured":"Pires DE, Ascher DB, Blundell TL. mCSM: predicting the effects of mutations in proteins using graph-based signatures. Bioinformatics. 2014;30(3):335\u201342.","journal-title":"Bioinformatics"},{"issue":"Suppl 4","key":"2923_CR15","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1186\/1471-2164-15-S4-S7","volume":"15","author":"M Giollo","year":"2014","unstructured":"Giollo M, Martin AJ, Walsh I, Ferrari C, Tosatto SC. NeEMO: a method using residue interaction networks to improve prediction of protein stability upon mutation. BMC Genomics. 2014;15(Suppl 4):S7.","journal-title":"BMC Genomics"},{"issue":"4","key":"2923_CR16","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/prot.20810","volume":"62","author":"J Cheng","year":"2006","unstructured":"Cheng J, Randall A, Baldi P. Prediction of protein stability changes for single-site mutations using support vector machines. Proteins. 2006;62(4):1125\u201332.","journal-title":"Proteins"},{"issue":"19","key":"2923_CR17","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1093\/bioinformatics\/btw361","volume":"32","author":"L Quan","year":"2016","unstructured":"Quan L, Lv Q, Zhang Y. STRUM: structure-based prediction of protein stability changes upon single-point mutation. Bioinformatics. 2016;32(19):2936\u201346.","journal-title":"Bioinformatics"},{"issue":"10","key":"2923_CR18","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1093\/bioinformatics\/btm100","volume":"23","author":"LT Huang","year":"2007","unstructured":"Huang LT, Gromiha MM, Ho SY. iPTREE-STAB: interpretable decision tree based method for predicting protein stability changes upon mutations. Bioinformatics. 2007;23(10):1292\u20133.","journal-title":"Bioinformatics"},{"issue":"Suppl 2","key":"2923_CR19","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1186\/1471-2164-11-S2-S5","volume":"11","author":"S Teng","year":"2010","unstructured":"Teng S, Srivastava AK, Wang L. Sequence feature-based prediction of protein stability changes upon amino acid substitutions. BMC Genomics. 2010;11(Suppl 2):S5.","journal-title":"BMC Genomics"},{"issue":"17","key":"2923_CR20","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.1093\/bioinformatics\/btv291","volume":"31","author":"P Fariselli","year":"2015","unstructured":"Fariselli P, Martelli PL, Savojardo C, Casadio R. INPS: predicting the impact of non-synonymous variations on protein stability from sequence. Bioinformatics. 2015;31(17):2816\u201321.","journal-title":"Bioinformatics"},{"issue":"6","key":"2923_CR21","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1016\/j.jmb.2016.01.012","volume":"428","author":"L Folkman","year":"2016","unstructured":"Folkman L, Stantic B, Sattar A, Zhou Y. EASE-MM: sequence-based prediction of mutation-induced stability changes with feature-based multiple models. J Mol Biol. 2016;428(6):1394\u2013405.","journal-title":"J Mol Biol"},{"issue":"Suppl 2","key":"2923_CR22","doi-asserted-by":"publisher","first-page":"ii54","DOI":"10.1093\/bioinformatics\/bti1109","volume":"21","author":"E Capriotti","year":"2005","unstructured":"Capriotti E, Fariselli P, Calabrese R, Casadio R. Predicting protein stability changes from sequences using support vector machines. Bioinformatics. 2005;21(Suppl 2):ii54\u20138.","journal-title":"Bioinformatics"},{"issue":"4","key":"2923_CR23","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.3390\/ijms19041009","volume":"19","author":"Yang Yang","year":"2018","unstructured":"Yang Y, Urolagin S, Niroula A, Ding X, Shen B, Vihinen M. PON-tstab: protein variant stability predictor. Importance of training data quality. Int J Mol Sci. 2018;19(4):.","journal-title":"International Journal of Molecular Sciences"},{"key":"2923_CR24","doi-asserted-by":"publisher","first-page":"W314","DOI":"10.1093\/nar\/gku411","volume":"42","author":"DE Pires","year":"2014","unstructured":"Pires DE, Ascher DB, Blundell TL. DUET: a server for predicting effects of mutations on protein stability using an integrated computational approach. Nucleic Acids Res. 2014;42(Web Server issue:W314\u20139.","journal-title":"Nucleic Acids Res"},{"issue":"Suppl 2","key":"2923_CR25","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1186\/1471-2105-14-S4-S5","volume":"14","author":"CW Chen","year":"2013","unstructured":"Chen CW, Lin J, Chu YW. iStable: off-the-shelf predictor integration for predicting protein stability changes. BMC bioinformatics. 2013;14(Suppl 2):S5.","journal-title":"BMC bioinformatics"},{"issue":"Database issue","key":"2923_CR26","doi-asserted-by":"publisher","first-page":"D204","DOI":"10.1093\/nar\/gkj103","volume":"34","author":"MD Kumar","year":"2006","unstructured":"Kumar MD, Bava KA, Gromiha MM, Prabakaran P, Kitajima K, Uedaira H, Sarai A. ProTherm and ProNIT: thermodynamic databases for proteins and protein-nucleic acid interactions. Nucleic Acids Res. 2006;34(Database issue):D204\u20136.","journal-title":"Nucleic Acids Res"},{"key":"2923_CR27","doi-asserted-by":"publisher","unstructured":"Montanucci L, Savojardo C, Martelli PL, Casadio R, Fariselli P. On the biases in predictions of protein stability changes upon variations: the INPS test case. Bioinformatics. 2018; \n                    https:\/\/doi.org\/10.1093\/bioinformatics\/bty979\n                    \n                  .","DOI":"10.1093\/bioinformatics\/bty979"},{"issue":"21","key":"2923_CR28","doi-asserted-by":"publisher","first-page":"3659","DOI":"10.1093\/bioinformatics\/bty348","volume":"34","author":"F Pucci","year":"2018","unstructured":"Pucci F, Bernaerts K, Kwasigroch JM, Rooman M. Quantification of biases in predictions of protein stability changes upon mutations. Bioinformatics. 2018;34(21):3659\u201365.","journal-title":"Bioinformatics"},{"issue":"21","key":"2923_CR29","doi-asserted-by":"publisher","first-page":"3653","DOI":"10.1093\/bioinformatics\/bty340","volume":"34","author":"DR Usmanova","year":"2018","unstructured":"Usmanova DR, Bogatyreva NS, Arino Bernad J, Eremina AA, Gorshkova AA, Kanevskiy GM, Lonishin LR, Meister AV, Yakupova AG, Kondrashov FA, et al. Self-consistency test reveals systematic bias in programs for prediction change of stability upon mutation. Bioinformatics. 2018;34(21):3653\u20138.","journal-title":"Bioinformatics"},{"key":"2923_CR30","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12859-015-0548-6","volume":"16","author":"J Laimer","year":"2015","unstructured":"Laimer J, Hofer H, Fritz M, Wegenkittl S, Lackner P. MAESTRO--multi agent stability prediction upon point mutations. BMC bioinformatics. 2015;16:116.","journal-title":"BMC bioinformatics"},{"issue":"3","key":"2923_CR31","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1002\/pro.5560060317","volume":"6","author":"J Skolnick","year":"1997","unstructured":"Skolnick J, Jaroszewski L, Kolinski A, Godzik A. Derivation and testing of pair potentials for protein folding. When is the quasichemical approximation correct? Protein Sci. 1997;6(3):676\u201388.","journal-title":"Protein Sci"},{"issue":"2","key":"2923_CR32","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1002\/prot.1075","volume":"44","author":"U Bastolla","year":"2001","unstructured":"Bastolla U, Farwer J, Knapp EW, Vendruscolo M. How to guarantee optimal stability for most representative structures in the protein data Bank. Proteins. 2001;44(2):79\u201396.","journal-title":"Proteins"},{"issue":"35","key":"2923_CR33","doi-asserted-by":"publisher","first-page":"14349","DOI":"10.1074\/jbc.M117.784165","volume":"292","author":"A Broom","year":"2017","unstructured":"Broom A, Jacobi Z, Trainor K, Meiering EM. Computational tools help improve protein stability but with a solubility tradeoff. J Biol Chem. 2017;292(35):14349\u201361.","journal-title":"J Biol Chem"},{"issue":"10 Pt A","key":"2923_CR34","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/j.bbapap.2015.06.002","volume":"1854","author":"KP Kepp","year":"2015","unstructured":"Kepp KP. Towards a \"Golden standard\" for computing globin stability: stability and structure sensitivity of myoglobin mutants. Biochim Biophys Acta. 2015;1854(10 Pt A):1239\u201348.","journal-title":"Biochim Biophys Acta"},{"issue":"9","key":"2923_CR35","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1093\/bioinformatics\/bty880","volume":"35","author":"L Montanucci","year":"2018","unstructured":"Montanucci L, Martelli PL, Ben-Tal N, Fariselli P. A natural upper bound to the accuracy of predicting protein stability changes upon mutations. Bioinformatics. 2018;35(9):1513\u20137.","journal-title":"Bioinformatics"},{"key":"2923_CR36","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1146\/annurev.biophys.29.1.291","volume":"29","author":"MA Marti-Renom","year":"2000","unstructured":"Marti-Renom MA, Stuart AC, Fiser A, Sanchez R, Melo F, Sali A. Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct. 2000;29:291\u2013325.","journal-title":"Annu Rev Biophys Biomol Struct"},{"issue":"15","key":"2923_CR37","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1016\/j.jmb.2017.12.007","volume":"430","author":"L Zimmermann","year":"2018","unstructured":"Zimmermann L, Stephens A, Nam SZ, Rau D, Kubler J, Lozajic M, Gabler F, Soding J, Lupas AN, Alva V. A completely Reimplemented MPI bioinformatics toolkit with a new HHpred server at its Core. J Mol Biol. 2018;430(15):2237\u201343.","journal-title":"J Mol Biol"},{"issue":"22","key":"2923_CR38","doi-asserted-by":"publisher","first-page":"10915","DOI":"10.1073\/pnas.89.22.10915","volume":"89","author":"S Henikoff","year":"1992","unstructured":"Henikoff S, Henikoff JG. Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A. 1992;89(22):10915\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"2923_CR39","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/0022-2836(82)90515-0","volume":"157","author":"J Kyte","year":"1982","unstructured":"Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982;157(1):105\u201332.","journal-title":"J Mol Biol"},{"issue":"12","key":"2923_CR40","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.1002\/bip.360221211","volume":"22","author":"W Kabsch","year":"1983","unstructured":"Kabsch W, Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983;22(12):2577\u2013637.","journal-title":"Biopolymers"},{"issue":"Database issue","key":"2923_CR41","doi-asserted-by":"publisher","first-page":"D364","DOI":"10.1093\/nar\/gku1028","volume":"43","author":"WG Touw","year":"2015","unstructured":"Touw WG, Baakman C, Black J, te Beek TA, Krieger E, Joosten RP, Vriend G. A series of PDB-related databanks for everyday needs. Nucleic Acids Res. 2015;43(Database issue):D364\u20138.","journal-title":"Nucleic Acids Res"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-2923-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12859-019-2923-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-2923-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T23:27:21Z","timestamp":1593646041000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-019-2923-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7]]},"references-count":41,"journal-issue":{"issue":"S14","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["2923"],"URL":"https:\/\/doi.org\/10.1186\/s12859-019-2923-1","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7]]},"assertion":[{"value":"3 July 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"335"}}