{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:31:10Z","timestamp":1780392670303,"version":"3.54.1"},"reference-count":97,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"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\/501100012331","name":"LEO Foundation","doi-asserted-by":"publisher","award":["LF17006"],"award-info":[{"award-number":["LF17006"]}],"id":[{"id":"10.13039\/501100012331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012331","name":"LEO Foundation","doi-asserted-by":"publisher","award":["LF17024"],"award-info":[{"award-number":["LF17024"]}],"id":[{"id":"10.13039\/501100012331","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Carlsberg Distinguished Fellowship","award":["CF18-0314"],"award-info":[{"award-number":["CF18-0314"]}]},{"DOI":"10.13039\/501100001732","name":"Danmarks Grundforskningsfond","doi-asserted-by":"publisher","award":["DNRF125"],"award-info":[{"award-number":["DNRF125"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NovoNordisk Fonden in Bioscience and Basic Biomedicine","award":["0065262"],"award-info":[{"award-number":["0065262"]}]},{"name":"Biotechnology-based Synthesis and Production","award":["17OC0027588"],"award-info":[{"award-number":["17OC0027588"]}]},{"DOI":"10.13039\/501100009910","name":"Hartmann Foundation","doi-asserted-by":"publisher","award":["A33877"],"award-info":[{"award-number":["A33877"]}],"id":[{"id":"10.13039\/501100009910","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:p>Mutations, which result in amino acid substitutions, influence the stability of proteins and their binding to biomolecules. A molecular understanding of the effects of protein mutations is both of biotechnological and medical relevance. Empirical free energy functions that quickly estimate the free energy change upon mutation (\u0394\u0394G) can be exploited for systematic screenings of proteins and protein complexes. In silico saturation mutagenesis can guide the design of new experiments or rationalize the consequences of known mutations. Often software such as FoldX, while fast and reliable, lack the necessary automation features to apply them in a high-throughput manner. We introduce MutateX, a software to automate the prediction of \u0394\u0394Gs associated with the systematic mutation of each residue within a protein, or protein complex to all other possible residue types, using the FoldX energy function. MutateX also supports \u0394\u0394G calculations over protein ensembles, upon post-translational modifications and in multimeric assemblies. At the heart of MutateX lies an automated pipeline engine that handles input preparation, parallelization and outputs publication-ready figures. We illustrate the MutateX protocol applied to different case studies. The results of the high-throughput scan provided by our tools can help in different applications, such as the analysis of disease-associated mutations, to complement experimental deep mutational scans, or assist the design of variants for industrial applications. MutateX is a collection of Python tools that relies on open-source libraries. It is available free of charge under the GNU General Public License from https:\/\/github.com\/ELELAB\/mutatex.<\/jats:p>","DOI":"10.1093\/bib\/bbac074","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T15:10:57Z","timestamp":1645024257000},"source":"Crossref","is-referenced-by-count":67,"title":["MutateX: an automated pipeline for\n                    <i>in silico<\/i>\n                    saturation mutagenesis of protein structures and structural ensembles"],"prefix":"10.1093","volume":"23","author":[{"given":"Matteo","family":"Tiberti","sequence":"first","affiliation":[{"name":"Cancer Structural Biology, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilde","family":"Terkelsen","sequence":"additional","affiliation":[{"name":"Cancer Structural Biology, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Degn","sequence":"additional","affiliation":[{"name":"Cancer Systems Biology, Section for Bioinformatics, Department of Health and Technology, Technical University of Denmark, 2800, Lyngby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Beltrame","sequence":"additional","affiliation":[{"name":"Cancer Structural Biology, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tycho Canter","family":"Cremers","sequence":"additional","affiliation":[{"name":"Cancer Structural Biology, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"da Piedade","sequence":"additional","affiliation":[{"name":"Cancer Structural Biology, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Di Marco","sequence":"additional","affiliation":[{"name":"Cancer Structural Biology, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Maiani","sequence":"additional","affiliation":[{"name":"Cancer Structural Biology, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7376-5894","authenticated-orcid":false,"given":"Elena","family":"Papaleo","sequence":"additional","affiliation":[{"name":"Cancer Structural Biology, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark"},{"name":"Cancer Systems Biology, Section for Bioinformatics, Department of Health and Technology, Technical University of Denmark, 2800, Lyngby, Denmark"},{"name":"Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"2022051813181302000_ref1","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0168-9525(01)02323-X","article-title":"Protein-protein interaction maps: a lead towards cellular functions","volume":"17","author":"Legrain","year":"2001","journal-title":"Trends Genet"},{"key":"2022051813181302000_ref2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/pmic.201500295","article-title":"Exploring the potential of public proteomics data","volume":"16","author":"Vaudel","year":"2015","journal-title":"Proteomics"},{"key":"2022051813181302000_ref3","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.copbio.2015.01.005","article-title":"Proteomics beyond large-scale protein expression analysis","volume":"34","author":"Boersema","year":"2015","journal-title":"Curr Opin Biotechnol"},{"key":"2022051813181302000_ref4","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.copbio.2018.01.009","article-title":"Quantitative -omic data empowers bottom-up systems biology","volume":"51","author":"Yurkovich","year":"2018","journal-title":"Curr Opin Biotechnol"},{"key":"2022051813181302000_ref5","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1021\/acs.analchem.5b04123","article-title":"Phosphoproteomics in the age of rapid and deep proteome profiling","volume":"88","author":"Riley","year":"2015","journal-title":"Anal Chem"},{"key":"2022051813181302000_ref6","doi-asserted-by":"crossref","first-page":"e3001207","DOI":"10.1371\/journal.pbio.3001207","article-title":"Pathogenic missense protein variants affect different functional pathways and proteomic features than healthy population variants","volume":"19","author":"Laddach","year":"2021","journal-title":"PLoS Biol"},{"key":"2022051813181302000_ref7","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.sbi.2017.12.006","article-title":"Genetic variants and protein\u2013protein interactions: a multidimensional network-centric view","volume":"50","author":"Laddach","year":"2018","journal-title":"Curr Opin Struct Biol"},{"key":"2022051813181302000_ref8","doi-asserted-by":"crossref","first-page":"D777","DOI":"10.1093\/nar\/gkw1121","article-title":"COSMIC: somatic cancer genetics at high-resolution","volume":"45","author":"Forbes","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2022051813181302000_ref9","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov"},{"key":"2022051813181302000_ref10","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41586-021-03822-7","article-title":"The mutational landscape of human somatic and germline cells","volume":"597","author":"Moore","year":"2021","journal-title":"Nature"},{"key":"2022051813181302000_ref11","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s12265-011-9259-1","article-title":"Meet me halfway: when genomics meets structural bioinformatics","volume":"4","author":"Gong","year":"2011","journal-title":"J Cardiovasc Transl Res"},{"key":"2022051813181302000_ref12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nmeth.4540","article-title":"Interactome INSIDER: a structural interactome browser for genomic studies","volume":"15","author":"Meyer","year":"2018","journal-title":"Nat Methods"},{"key":"2022051813181302000_ref13","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/s41586-021-03771-1","article-title":"In silico saturation mutagenesis of cancer genes","volume":"596","author":"Mui\u00f1os","year":"2021","journal-title":"Nature"},{"key":"2022051813181302000_ref14","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/humu.20938","article-title":"Pathogenic or not? And if so, then how? Studying the effects of missense mutations using bioinformatics methods","volume":"30","author":"Thusberg","year":"2009","journal-title":"Hum Mutat"},{"key":"2022051813181302000_ref15","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1093\/nar\/gkr407","article-title":"Predicting the functional impact of protein mutations: application to cancer genomics","volume":"39","author":"Reva","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2022051813181302000_ref16","doi-asserted-by":"crossref","first-page":"46","DOI":"10.5496\/wjmg.v5.i3.46","article-title":"Value of predictive bioinformatics in inherited metabolic diseases","volume":"5","author":"Timson","year":"2015","journal-title":"World J Med Genet"},{"key":"2022051813181302000_ref17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S1367-5931(00)00182-4","article-title":"Improved biocatalysts by directed evolution and rational protein design","volume":"5","author":"Bornscheuer","year":"2001","journal-title":"Curr Opin Chem Biol"},{"key":"2022051813181302000_ref18","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.cbpa.2010.11.011","article-title":"Status of protein engineering for biocatalysts: how to design an industrially useful biocatalyst","volume":"15","author":"Bommarius","year":"2011","journal-title":"Curr Opin Chem Biol"},{"key":"2022051813181302000_ref19","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/hmg\/ddv625","article-title":"Integrating population variation and protein structural analysis to improve clinical interpretation of missense variation: application to the WD40 domain","volume":"25","author":"Laskowski","year":"2016","journal-title":"Hum Mol Genet"},{"key":"2022051813181302000_ref20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nrg2273","article-title":"Understanding the molecular machinery of genetics through 3D structures","volume":"9","author":"Laskowski","year":"2008","journal-title":"Nat Rev Genet"},{"key":"2022051813181302000_ref21","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.tibs.2019.01.003","article-title":"Biophysical and mechanistic models for disease-causing protein variants","volume":"44","author":"Stein","year":"2019","journal-title":"Trends Biochem Sci"},{"key":"2022051813181302000_ref22","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.cbpa.2010.08.007","article-title":"Choreographing an enzyme\u2019s dance","volume":"14","author":"Villali","year":"2011","journal-title":"Curr Opin Chem Biol"},{"key":"2022051813181302000_ref23","doi-asserted-by":"crossref","first-page":"6679","DOI":"10.1073\/pnas.0408930102","article-title":"Molecular dynamics and protein function","volume":"102","author":"Karplus","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022051813181302000_ref24","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/nchembio.238","article-title":"NMR spectroscopy brings invisible protein states into focus","volume":"5","author":"Baldwin","year":"2009","journal-title":"Nat Chem Biol"},{"key":"2022051813181302000_ref25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.sbi.2007.01.002","article-title":"Determination of conformationally heterogeneous states of proteins","volume":"17","author":"Vendruscolo","year":"2007","journal-title":"Curr Opin Struct Biol"},{"key":"2022051813181302000_ref26","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.pnmrs.2014.11.001","article-title":"NMR studies of dynamic biomolecular conformational ensembles","volume":"84\u201385","author":"Torchia","year":"2015","journal-title":"Prog Nucl Magn Reson Spectrosc"},{"key":"2022051813181302000_ref27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jmr.2013.11.016","article-title":"Towards a true protein movie: a perspective on the potential impact of the ensemble-based structure determination using exact NOEs","volume":"241","author":"V\u00f6geli","year":"2014","journal-title":"J Magn Reson"},{"key":"2022051813181302000_ref28","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1146\/annurev-biophys-042910-155245","article-title":"Biomolecular simulation: a computational microscope for molecular biology","volume":"41","author":"Dror","year":"2012","journal-title":"Annu Rev Biophys"},{"key":"2022051813181302000_ref29","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1021\/acs.chemrev.5b00623","article-title":"The role of protein loops and linkers in conformational dynamics and allostery","volume":"116","author":"Papaleo","year":"2016","journal-title":"Chem Rev"},{"key":"2022051813181302000_ref30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmolb.2015.00028","article-title":"Integrating atomistic molecular dynamics simulations, experiments, and network analysis to study protein dynamics: strength in unity","volume":"2","author":"Papaleo","year":"2015","journal-title":"Front Mol Biosci"},{"key":"2022051813181302000_ref31","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s10858-012-9609-6","article-title":"Combining NMR ensembles and molecular dynamics simulations provides more realistic models of protein structures in solution and leads to better chemical shift prediction","volume":"52","author":"Lehtivarjo","year":"2012","journal-title":"J Biomol NMR"},{"key":"2022051813181302000_ref32","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nature03199","article-title":"Simultaneous determination of protein structure and dynamics","volume":"433","author":"Lindorff-Larsen","year":"2005","journal-title":"Nature"},{"key":"2022051813181302000_ref33","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/wcms.1093","article-title":"Synergistic use of NMR and MD simulations to study the structural heterogeneity of proteins","volume":"2","author":"Esteban-Mart\u00edn","year":"2012","journal-title":"Wiley Interdiscip Rev Comput Mol Sci"},{"key":"2022051813181302000_ref34","doi-asserted-by":"crossref","first-page":"e1410","DOI":"10.1002\/wcms.1410","article-title":"Finding the \u0394\u0394G spot: are predictors of binding affinity changes upon mutations in protein\u2013protein interactions ready for it?","volume":"9","author":"Geng","year":"2019","journal-title":"Wiley Interdiscip Rev Comput Mol Sci"},{"key":"2022051813181302000_ref35","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/humu.21445","article-title":"Performance of mutation pathogenicity prediction methods on missense variants","volume":"32","author":"Thusberg","year":"2011","journal-title":"Hum Mutat"},{"key":"2022051813181302000_ref36","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/humu.21242","article-title":"Performance of protein stability predictors","volume":"31","author":"Khan","year":"2010","journal-title":"Hum Mutat"},{"key":"2022051813181302000_ref37","doi-asserted-by":"crossref","first-page":"16367","DOI":"10.1073\/pnas.1903888116","article-title":"Protein stability engineering insights revealed by domain-wide comprehensive mutagenesis","volume":"116","author":"Nisthal","year":"2019","journal-title":"Proc Natl Acad Sci"},{"key":"2022051813181302000_ref38","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/protein\/gzp030","article-title":"Assessing computational methods for predicting protein stability upon mutation: good on average but not in the details","volume":"22","author":"Potapov","year":"2009","journal-title":"Protein Eng Des Sel"},{"key":"2022051813181302000_ref39","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0022-2836(02)00442-4","article-title":"Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations","volume":"320","author":"Guerois","year":"2002","journal-title":"J Mol Biol"},{"key":"2022051813181302000_ref40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.csbj.2018.01.002","article-title":"FoldX as protein engineering tool: better than random based approaches?","volume":"16","author":"Bu\u00df","year":"2018","journal-title":"Comput Struct Biotechnol J"},{"key":"2022051813181302000_ref41","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/humu.23707","article-title":"Toward mechanistic models for genotype-phenotype correlations in phenylketonuria using protein stability calculations","volume":"40","author":"Scheller","year":"2019","journal-title":"Hum Mutat"},{"key":"2022051813181302000_ref42","doi-asserted-by":"crossref","first-page":"e1006739","DOI":"10.1371\/journal.pgen.1006739","article-title":"Predicting the impact of lynch syndrome-causing missense mutations from structural calculations","volume":"13","author":"Nielsen","year":"2017","journal-title":"PLoS Genet"},{"key":"2022051813181302000_ref43","doi-asserted-by":"crossref","first-page":"e1000052","DOI":"10.1371\/journal.pcbi.1000052","article-title":"Genome-wide prediction of SH2 domain targets using structural information and the FoldX algorithm","volume":"4","author":"S\u00e1nchez","year":"2008","journal-title":"PLoS Comput Biol"},{"key":"2022051813181302000_ref44","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1021\/ci300398z","article-title":"Accurate stabilities of laccase mutants predicted with a modified FoldX protocol","volume":"52","author":"Christensen","year":"2012","journal-title":"J Chem Inf Model"},{"key":"2022051813181302000_ref45","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1016\/j.bbapap.2014.08.011","article-title":"The role of salt bridges on the temperature adaptation of aqualysin I, a thermostable subtilisin-like proteinase","volume":"1844","author":"J\u00f3nsd\u00f3ttir","year":"2014","journal-title":"Biochim Biophys Acta Proteins Proteomics"},{"key":"2022051813181302000_ref46","doi-asserted-by":"crossref","first-page":"bbab555","DOI":"10.1093\/bib\/bbab555","article-title":"Predicting protein stability changes upon single-point mutation: a thorough comparison of the available tools on a new dataset","volume":"1\u201312","author":"Pancotti","year":"2022","journal-title":"Brief Bioinform"},{"key":"2022051813181302000_ref47","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1093\/bioinformatics\/bty340","article-title":"Self-consistency test reveals systematic bias in programs for prediction change of stability upon mutation","volume":"34","author":"Usmanova","year":"2018","journal-title":"Bioinformatics"},{"key":"2022051813181302000_ref48","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1093\/bioinformatics\/bty348","article-title":"Quantification of biases in predictions of protein stability changes upon mutations","volume":"34","author":"Pucci","year":"2018","journal-title":"Bioinformatics"},{"key":"2022051813181302000_ref49","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12859-021-04030-w","article-title":"A base measure of precision for protein stability predictors: structural sensitivity","volume":"22","author":"Caldararu","year":"2021","journal-title":"BMC Bioinformatics"},{"issue":"20","key":"2022051813181302000_ref50","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.1093\/bioinformatics\/btz184","article-title":"FoldX 5.0: working with RNA, small molecules and a new graphical interface","volume":"35","author":"Delgado","year":"2019","journal-title":"Bioinformatics"},{"key":"2022051813181302000_ref51","first-page":"1","article-title":"xPyder: a PyMOL plugin to analyze coupled residues and their networks in protein structures","volume":"279","author":"Pasi","year":"2012","journal-title":"J Chem Inf Model"},{"key":"2022051813181302000_ref52","doi-asserted-by":"crossref","first-page":"D204","DOI":"10.1093\/nar\/gkj103","article-title":"ProTherm and ProNIT: thermodynamic databases for proteins and protein-nucleic acid interactions","volume":"34","author":"Kumar","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"2022051813181302000_ref53","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ymeth.2015.02.009","article-title":"PTEN: a yin-yang master regulator protein in health and disease","volume":"77\u201378","author":"Pulido","year":"2015","journal-title":"Methods"},{"key":"2022051813181302000_ref54","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1242\/jcs.114.13.2375","article-title":"Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis","volume":"114","author":"Yamada","year":"2001","journal-title":"J Cell Sci"},{"key":"2022051813181302000_ref55","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev.pathol.4.110807.092311","article-title":"PTEN and the PI3-kinase pathway in cancer","volume":"4","author":"Chalhoub","year":"2009","journal-title":"Annu Rev Pathol Mech Dis"},{"key":"2022051813181302000_ref56","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/B978-0-12-819132-3.00005-1","article-title":"Classifying disease-associated variants using measures of protein activity and stability","author":"Jepsen","year":"2020","journal-title":"Protein Homeost Dis"},{"key":"2022051813181302000_ref57","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0092-8674(00)81663-3","article-title":"Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association","volume":"99","author":"Lee","year":"1999","journal-title":"Cell"},{"key":"2022051813181302000_ref58","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1146\/annurev-biochem-060815-014710","article-title":"The p53 pathway: origins, inactivation in cancer, and emerging therapeutic approaches","volume":"85","author":"Joerger","year":"2016","journal-title":"Annu Rev Biochem"},{"key":"2022051813181302000_ref59","first-page":"375","article-title":"Mutant p53: multiple mechanisms define biologic activity in cancer","volume":"85","author":"Kim","year":"2015","journal-title":"Front Oncol"},{"key":"2022051813181302000_ref60","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1101\/gad.190678.112","article-title":"Mutant p53: one name, many proteins","volume":"26","author":"Freed-pastor","year":"2012","journal-title":"Genes Dev"},{"key":"2022051813181302000_ref61","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/35042675","article-title":"Surfing the p53 network","volume":"408","author":"Vogelstein","year":"2000","journal-title":"Nature"},{"key":"2022051813181302000_ref62","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1146\/annurev.biochem.77.060806.091238","article-title":"Structural biology of the tumor suppressor p53","volume":"77","author":"Joerger","year":"2008","journal-title":"Annu Rev Biochem"},{"key":"2022051813181302000_ref63","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.sbi.2009.02.003","article-title":"Structural biology of the p53 tumour suppressor","volume":"19","author":"Okorokov","year":"2009","journal-title":"Curr Opin Struct Biol"},{"key":"2022051813181302000_ref64","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.molcel.2006.05.015","article-title":"Structural basis of DNA recognition by p53 tetramers","volume":"22","author":"Kitayner","year":"2006","journal-title":"Mol Cell"},{"key":"2022051813181302000_ref65","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.str.2009.11.011","article-title":"Crystal structure of the p53 Core domain bound to a full consensus site as a self-assembled tetramer","volume":"18","author":"Chen","year":"2010","journal-title":"Structure"},{"key":"2022051813181302000_ref66","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0092-8674(00)81688-8","article-title":"Signaling - 2000 and beyond","volume":"100","author":"Hunter","year":"2000","journal-title":"Cell"},{"key":"2022051813181302000_ref67","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1038\/srep02651","article-title":"The mutational landscape of phosphorylation signaling in cancer","volume":"3","author":"Reimand","year":"2013","journal-title":"Sci Rep"},{"key":"2022051813181302000_ref68","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nrm759","article-title":"Phosphotyrosine-binding domains in signal transduction","volume":"3","author":"Yaffe","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2022051813181302000_ref69","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.molcel.2006.06.001","article-title":"The human and mouse complement of SH2 domain proteins\u2014establishing the boundaries of phosphotyrosine signaling","volume":"22","author":"Liu","year":"2006","journal-title":"Mol Cell"},{"key":"2022051813181302000_ref70","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.molcel.2007.05.031","article-title":"High-throughput phosphotyrosine profiling using SH2 domains","volume":"26","author":"Machida","year":"2007","journal-title":"Mol Cell"},{"key":"2022051813181302000_ref71","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.celrep.2013.03.001","article-title":"The SH2 domain interaction landscape","volume":"3","author":"Tinti","year":"2013","journal-title":"Cell Rep"},{"key":"2022051813181302000_ref72","doi-asserted-by":"crossref","first-page":"4942","DOI":"10.1074\/jbc.M116.757518","article-title":"Both intrinsic substrate preference and network context contribute to substrate selection of classical tyrosine phosphatases","volume":"292","author":"Palma","year":"2017","journal-title":"J Biol Chem"},{"key":"2022051813181302000_ref73","doi-asserted-by":"crossref","first-page":"14053","DOI":"10.1073\/pnas.212518799","article-title":"Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide","volume":"99","author":"Donaldson","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022051813181302000_ref74","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1006\/jmbi.2001.5299","article-title":"Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new high-affinity inhibitor","volume":"315","author":"Nioche","year":"2002","journal-title":"J Mol Biol"},{"key":"2022051813181302000_ref75","doi-asserted-by":"crossref","first-page":"7637","DOI":"10.1021\/bi200439v","article-title":"Simultaneous binding of two peptidyl ligands by a Src homology 2 domain","volume":"50","author":"Zhang","year":"2011","journal-title":"Biochemistry"},{"key":"2022051813181302000_ref76","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.jmb.2011.03.047","article-title":"Interaction of the p53 DNA-binding domain with its n-terminal extension modulates the stability of the p53 tetramer","volume":"409","author":"Natan","year":"2011","journal-title":"J Mol Biol"},{"key":"2022051813181302000_ref77","first-page":"9096","article-title":"DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions","volume":"44","author":"Lambrughi","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2022051813181302000_ref78","doi-asserted-by":"crossref","first-page":"D475","DOI":"10.1093\/nar\/gkaa925","article-title":"ThermoMutDB: a thermodynamic database for missense mutations","volume":"49","author":"Xavier","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2022051813181302000_ref79","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.abn7760","article-title":"SARS-CoV-2 omicron variant: antibody evasion and cryo-EM structure of spike protein\u2013ACE2 complex","volume":"375","author":"Mannar","year":"2022","journal-title":"Science"},{"key":"2022051813181302000_ref80","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.cell.2020.08.012","article-title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","volume":"182","author":"Starr","year":"2020","journal-title":"Cell"},{"key":"2022051813181302000_ref81","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.cell.2020.03.045","article-title":"Structural and functional basis of SARS-CoV-2 entry by using human ACE2","volume":"181","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"2022051813181302000_ref82","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1038\/s41564-021-00954-4","article-title":"SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution","volume":"6","author":"Zahradn\u00edk","year":"2021","journal-title":"Nat Microbiol"},{"key":"2022051813181302000_ref83","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1016\/j.bbapap.2014.09.018","article-title":"Structural investigation of the cold-adapted acylaminoacyl peptidase from Sporosarcina psychrophila by atomistic simulations and biophysical methods","volume":"1844","author":"Papaleo","year":"2014","journal-title":"Biochim Biophys Acta Proteins Proteomics"},{"key":"2022051813181302000_ref84","doi-asserted-by":"crossref","first-page":"21141","DOI":"10.1074\/jbc.M115.662312","article-title":"A two-step protein quality control pathway for a misfolded DJ-1 variant in fission yeast","volume":"290","author":"Mathiassen","year":"2015","journal-title":"J Biol Chem"},{"key":"2022051813181302000_ref85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmolb.2016.00078","article-title":"The mutational landscape of the oncogenic MZF1 SCAN domain in cancer","volume":"3","author":"Nygaard","year":"2016","journal-title":"Front Mol Biosci"},{"key":"2022051813181302000_ref86","doi-asserted-by":"crossref","first-page":"D941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: the catalogue of somatic mutations in cancer","volume":"47","author":"Tate","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2022051813181302000_ref87","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.sbi.2020.01.010","article-title":"Allosteric drugs and mutations: chances, challenges, and necessity","volume":"62","author":"Guarnera","year":"2020","journal-title":"Curr Opin Struct Biol"},{"key":"2022051813181302000_ref88","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12551-018-0496-2","article-title":"Precision medicine review: rare driver mutations and their biophysical classification","volume":"11","author":"Nussinov","year":"2019","journal-title":"Biophys Rev"},{"key":"2022051813181302000_ref89","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.sbi.2015.01.004","article-title":"\u2018Latent drivers\u2019 expand the cancer mutational landscape","volume":"32","author":"Nussinov","year":"2015","journal-title":"Curr Opin Struct Biol"},{"key":"2022051813181302000_ref90","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1080\/15548627.2020.1847443","article-title":"The conformational and mutational landscape of the ubiquitin-like marker for autophagosome formation in cancer","volume":"17","author":"Fas","year":"2021","journal-title":"Autophagy"},{"key":"2022051813181302000_ref91","doi-asserted-by":"crossref","first-page":"14874","DOI":"10.1038\/s41598-020-71527-4","article-title":"A pan-cancer assessment of alterations of the kinase domain of ULK1, an upstream regulator of autophagy","volume":"10","author":"Kumar","year":"2020","journal-title":"Sci Rep"},{"key":"2022051813181302000_ref92","doi-asserted-by":"crossref","first-page":"4","DOI":"10.2174\/1389203716666150923105727","article-title":"Protein structure and function: looking through the network of side-chain interactions","volume":"17","author":"Bhattacharyya","year":"2016","journal-title":"Curr Protein Pept Sci"},{"key":"2022051813181302000_ref93","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1021\/ci400639r","article-title":"PyInteraph: a framework for the analysis of interaction networks in structural ensembles of proteins","volume":"54","author":"Tiberti","year":"2014","journal-title":"J Chem Inf Model"},{"key":"2022051813181302000_ref94","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.str.2019.01.014","article-title":"Toward comprehensive allosteric control over protein activity","volume":"27","author":"Guarnera","year":"2019","journal-title":"Structure"},{"key":"2022051813181302000_ref95","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1002\/bit.26531","article-title":"Computer-assisted engineering of hyperstable fibroblast growth factor 2","volume":"115","author":"Dvorak","year":"2018","journal-title":"Biotechnol Bioeng"},{"key":"2022051813181302000_ref96","doi-asserted-by":"crossref","first-page":"e1003129","DOI":"10.1371\/journal.pcbi.1003129","article-title":"Engineering a more thermostable blue light photo receptor Bacillus subtilis YtvA LOV domain by a computer aided rational design method","volume":"9","author":"Song","year":"2013","journal-title":"PLoS Comput Biol"},{"key":"2022051813181302000_ref97","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/protein\/gzv004","article-title":"Increasing the stability of the bacteriophage endolysin PlyC using rationale-based FoldX computational modeling","volume":"28","author":"Heselpoth","year":"2015","journal-title":"Protein Eng Des Sel"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/23\/3\/bbac074\/43745752\/bbac074.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/23\/3\/bbac074\/43745752\/bbac074.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T09:27:51Z","timestamp":1652866071000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbac074\/6552273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,22]]},"references-count":97,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,5,13]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbac074","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/824938","asserted-by":"object"}]},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5]]},"published":{"date-parts":[[2022,3,22]]},"article-number":"bbac074"}}