{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T06:44:15Z","timestamp":1769841855728,"version":"3.49.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Department of Science and Technology, India","award":["EMR\/2016\/001476"],"award-info":[{"award-number":["EMR\/2016\/001476"]}]},{"name":"Ministry of Human Resources Development"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Protein\u2013protein interactions are essential for the cell and mediate various functions. However, mutations can disrupt these interactions and may cause diseases. Currently available computational methods require a complex structure as input for predicting the change in binding affinity. Further, they have not included the functional class information for the protein\u2013protein complex. To address this, we have developed a method, ProAffiMuSeq, which predicts the change in binding free energy using sequence-based features and functional class.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our method shows an average correlation between predicted and experimentally determined \u0394\u0394G of 0.73 and mean absolute error (MAE) of 0.86 kcal\/mol in 10-fold cross-validation and correlation of 0.75 with MAE of 0.94 kcal\/mol in the test dataset. ProAffiMuSeq was also tested on an external validation set and showed results comparable to structure-based methods. Our method can be used for large-scale analysis of disease-causing mutations in protein\u2013protein complexes without structural information.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Users can access the method at https:\/\/web.iitm.ac.in\/bioinfo2\/proaffimuseq\/.<\/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               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz829","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T12:10:55Z","timestamp":1573474255000},"page":"1725-1730","source":"Crossref","is-referenced-by-count":38,"title":["ProAffiMuSeq: sequence-based method to predict the binding free energy change of protein\u2013protein complexes upon mutation using functional classification"],"prefix":"10.1093","volume":"36","author":[{"given":"Sherlyn","family":"Jemimah","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras , Chennai 600036, India"}]},{"given":"Masakazu","family":"Sekijima","sequence":"additional","affiliation":[{"name":"Advanced Computational Drug Discovery Unit, Tokyo Institute of Technology , Midori-ku, Kanagawa 226-8503, Yokohama, Japan"}]},{"given":"M Michael","family":"Gromiha","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras , Chennai 600036, India"},{"name":"Advanced Computational Drug Discovery Unit, Tokyo Tech World Research Hub Initiative (WRHI), Institute of Innovative Research, Tokyo Institute of Technology , Midori-ku, Kanagawa 226-8503, Yokohama, Japan"}]}],"member":"286","published-online":{"date-parts":[[2019,11,12]]},"reference":[{"key":"2023060911580627400_btz829-B1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.mrfmmm.2015.07.005","article-title":"Discrimination of driver and passenger mutations in epidermal growth factor receptor in cancer","volume":"780","author":"Anoosha","year":"2015","journal-title":"Mutat. Res"},{"key":"2023060911580627400_btz829-B2","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1021\/acs.jpcb.7b11367","article-title":"Flex ddG: Rosetta ensemble-based estimation of changes in protein-protein binding affinity upon mutation","volume":"122","author":"Barlow","year":"2018","journal-title":"J. Phys. Chem. B"},{"key":"2023060911580627400_btz829-B3","doi-asserted-by":"crossref","first-page":"e107353.","DOI":"10.1371\/journal.pone.0107353","article-title":"Combining structural modeling with ensemble machine learning to accurately predict protein fold stability and binding affinity effects upon mutation","volume":"9","author":"Berliner","year":"2014","journal-title":"PLoS One"},{"key":"2023060911580627400_btz829-B4","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1093\/bioinformatics\/btv091","article-title":"Folding RaCe: a robust method for predicting changes in protein folding rates upon point mutations","volume":"31","author":"Chaudhary","year":"2015","journal-title":"Bioinformatics"},{"key":"2023060911580627400_btz829-B5","doi-asserted-by":"crossref","first-page":"e86738.","DOI":"10.1371\/journal.pone.0086738","article-title":"Non-redundant unique interface structures as templates for modeling protein interactions","volume":"9","author":"Cukuroglu","year":"2014","journal-title":"PLoS One"},{"key":"2023060911580627400_btz829-B6","doi-asserted-by":"crossref","first-page":"W333","DOI":"10.1093\/nar\/gkt450","article-title":"BeAtMuSiC: prediction of changes in protein-protein binding affinity on mutations","volume":"41","author":"Dehouck","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2023060911580627400_btz829-B7","doi-asserted-by":"crossref","first-page":"25406","DOI":"10.1038\/srep25406","article-title":"Modeling and fitting protein-protein complexes to predict change of binding energy","volume":"6","author":"Dourado","year":"2016","journal-title":"Sci. Rep"},{"key":"2023060911580627400_btz829-B8","doi-asserted-by":"crossref","first-page":"D805","DOI":"10.1093\/nar\/gku1075","article-title":"COSMIC: exploring the world\u2019s knowledge of somatic mutations in human cancer","volume":"43","author":"Forbes","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023060911580627400_btz829-B9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/prot.25630","article-title":"iSEE: interface structure, evolution, and energy-based machine learning predictor of binding affinity changes upon mutations","volume":"87","author":"Geng","year":"2019","journal-title":"Proteins"},{"key":"2023060911580627400_btz829-B10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-1-4939-3572-7_4","article-title":"Applications of protein thermodynamic database for understanding protein mutant stability and designing stable mutants","volume":"1415","author":"Gromiha","year":"2016","journal-title":"Methods Mol. Biol"},{"key":"2023060911580627400_btz829-B11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.sbi.2016.10.016","article-title":"Protein-protein interactions: scoring schemes and binding affinity","volume":"44","author":"Gromiha","year":"2017","journal-title":"Curr. Opin. Struct. Biol"},{"key":"2023060911580627400_btz829-B12","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/1097-0282(2000)55:5<399::AID-BIP1014>3.0.CO;2-9","article-title":"Identification of the ligand-binding site of the BMP type IA receptor for BMP-4","volume":"55","author":"Hatta","year":"2000","journal-title":"Biopolymers"},{"key":"2023060911580627400_btz829-B151","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1093\/bioinformatics\/bty635","article-title":"SKEMPI 2.0: an updated benchmark of changes in protein-protein binding energy, kinetics and thermodynamics upon mutation","volume":"35","author":"Jankauskaite","year":"2019","journal-title":"Bioinformatics"},{"key":"2023060911580627400_btz829-B13","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1002\/prot.25472","article-title":"Exploring additivity effects of double mutations on the binding affinity of protein-protein complexes","volume":"86","author":"Jemimah","year":"2018","journal-title":"Proteins"},{"key":"2023060911580627400_btz829-B14","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1093\/bioinformatics\/btx312","article-title":"PROXiMATE: a database of mutant protein-protein complex thermodynamics and kinetics","volume":"33","author":"Jemimah","year":"2017","journal-title":"Bioinformatics"},{"key":"2023060911580627400_btz829-B15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1073\/pnas.93.1.13","article-title":"Principles of protein-protein interactions","volume":"93","author":"Jones","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023060911580627400_btz829-B16","doi-asserted-by":"crossref","first-page":"D202","DOI":"10.1093\/nar\/gkm998","article-title":"AAindex: amino acid index database, progress report 2008","volume":"36","author":"Kawashima","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2023060911580627400_btz829-B17","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1021\/cr040409x","article-title":"Principles of protein-protein interactions: what are the preferred ways for proteins to interact?","volume":"108","author":"Keskin","year":"2008","journal-title":"Chem. Rev"},{"key":"2023060911580627400_btz829-B18","doi-asserted-by":"crossref","first-page":"9223","DOI":"10.1073\/pnas.0401160101","article-title":"Electrostatically optimized Ras-binding Ral guanine dissociation stimulator mutants increase the rate of association by stabilizing the encounter complex","volume":"101","author":"Kiel","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023060911580627400_btz829-B19","doi-asserted-by":"crossref","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","article-title":"ClinVar: public archive of interpretations of clinically relevant variants","volume":"44","author":"Landrum","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023060911580627400_btz829-B20","doi-asserted-by":"crossref","first-page":"W494","DOI":"10.1093\/nar\/gkw374","article-title":"MutaBind estimates and interprets the effects of sequence variants on protein-protein interactions","volume":"44","author":"Li","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023060911580627400_btz829-B21","doi-asserted-by":"crossref","first-page":"51.","DOI":"10.1186\/1471-2105-9-51","article-title":"The contrasting properties of conservation and correlated phylogeny in protein functional residue prediction","volume":"9","author":"Manning","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2023060911580627400_btz829-B22","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera - a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem"},{"key":"2023060911580627400_btz829-B23","doi-asserted-by":"crossref","first-page":"e1004276.","DOI":"10.1371\/journal.pcbi.1004276","article-title":"Predicting binding free energy change caused by point mutations with knowledge-modified MM\/PBSA method","volume":"11","author":"Petukh","year":"2015","journal-title":"PLoS Comput. Biol"},{"key":"2023060911580627400_btz829-B24","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/bioinformatics\/btt691","article-title":"mCSM: predicting the effects of mutations in proteins using graph-based signatures","volume":"30","author":"Pires","year":"2014","journal-title":"Bioinformatics"},{"key":"2023060911580627400_btz829-B25","doi-asserted-by":"crossref","first-page":"W469","DOI":"10.1093\/nar\/gkw458","article-title":"mCSM-AB: a web server for predicting antibody-antigen affinity changes upon mutation with graph-based signatures","volume":"44","author":"Pires","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023060911580627400_btz829-B26","doi-asserted-by":"crossref","first-page":"6310","DOI":"10.1021\/bi00019a008","article-title":"Energetic contributions and topographical organization of ligand binding residues of tissue factor","volume":"34","author":"Ruf","year":"1995","journal-title":"Biochemistry"},{"key":"2023060911580627400_btz829-B27","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1002\/pro.2736","article-title":"Linking structural features of protein complexes and biological function","volume":"24","author":"Sowmya","year":"2015","journal-title":"Protein Sci"},{"key":"2023060911580627400_btz829-B28","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/prot.10146","article-title":"Scoring residue conservation","volume":"48","author":"Valdar","year":"2002","journal-title":"Proteins"},{"key":"2023060911580627400_btz829-B29","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.jmb.2016.11.022","article-title":"BindProfX: assessing mutation-induced binding affinity change by protein interface profiles with pseudo-counts","volume":"429","author":"Xiong","year":"2017","journal-title":"J. Mol. Biol"},{"key":"2023060911580627400_btz829-B30","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1093\/bioinformatics\/btu580","article-title":"Protein-protein binding affinity prediction from amino acid sequence","volume":"30","author":"Yugandhar","year":"2014","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btz829\/31498613\/btz829.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/36\/6\/1725\/50554187\/bioinformatics_36_6_1725.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/36\/6\/1725\/50554187\/bioinformatics_36_6_1725.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T11:58:54Z","timestamp":1686311934000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/36\/6\/1725\/5622758"}},"subtitle":[],"editor":[{"given":"John","family":"Hancock","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2019,11,12]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btz829","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,3,15]]},"published":{"date-parts":[[2019,11,12]]}}}