{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T01:19:05Z","timestamp":1786065545362,"version":"3.56.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"W1","license":[{"start":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T00:00:00Z","timestamp":1556841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness","award":["BIO2016-78310-R"],"award-info":[{"award-number":["BIO2016-78310-R"]}]},{"DOI":"10.13039\/501100004442","name":"National Science Center","doi-asserted-by":"publisher","award":["MAESTRO2014\/14\/A\/ST6\/00088"],"award-info":[{"award-number":["MAESTRO2014\/14\/A\/ST6\/00088"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Protein aggregation is a hallmark of a growing number of human disorders and constitutes a major bottleneck in the manufacturing of therapeutic proteins. Therefore, there is a strong need of in-silico methods that can anticipate the aggregative properties of protein variants linked to disease and assist the engineering of soluble protein-based drugs. A few years ago, we developed a method for structure-based prediction of aggregation properties that takes into account the dynamic fluctuations of proteins. The method has been made available as the Aggrescan3D (A3D) web server and applied in numerous studies of protein structure-aggregation relationship. Here, we present a major update of the A3D web server to version 2.0. The new features include: extension of dynamic calculations to significantly larger and multimeric proteins, simultaneous prediction of changes in protein solubility and stability upon mutation, rapid screening for functional protein variants with improved solubility, a REST-ful service to incorporate A3D calculations in automatic pipelines, and a new, enhanced web server interface. A3D 2.0 is freely available at: http:\/\/biocomp.chem.uw.edu.pl\/A3D2\/<\/jats:p>","DOI":"10.1093\/nar\/gkz321","type":"journal-article","created":{"date-parts":[[2019,4,21]],"date-time":"2019-04-21T07:06:53Z","timestamp":1555830413000},"page":"W300-W307","source":"Crossref","is-referenced-by-count":188,"title":["Aggrescan3D (A3D) 2.0: prediction and engineering of protein solubility"],"prefix":"10.1093","volume":"47","author":[{"given":"Aleksander","family":"Kuriata","sequence":"first","affiliation":[{"name":"Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, 02-089 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Institut de Biotecnologia i Biomedicina and Departament de Bioqu\u00edmica I Biologia Molecular Universitat Aut\u00f2noma de Barcelona, Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Pujols","sequence":"additional","affiliation":[{"name":"Institut de Biotecnologia i Biomedicina and Departament de Bioqu\u00edmica I Biologia Molecular Universitat Aut\u00f2noma de Barcelona, Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Kurcinski","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, 02-089 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7623-0935","authenticated-orcid":false,"given":"Sebastian","family":"Kmiecik","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, 02-089 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Ventura","sequence":"additional","affiliation":[{"name":"Institut de Biotecnologia i Biomedicina and Departament de Bioqu\u00edmica I Biologia Molecular Universitat Aut\u00f2noma de Barcelona, Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,3]]},"reference":[{"key":"2019062808125162200_B1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1146\/annurev-biochem-061516-045115","article-title":"Protein misfolding, amyloid formation, and human disease: a summary of progress over the last decade","volume":"86","author":"Chiti","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"2019062808125162200_B2","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/j.biocel.2012.05.023","article-title":"Protein aggregation: mechanisms and functional consequences","volume":"44","author":"Invernizzi","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2019062808125162200_B3","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.tibtech.2013.05.004","article-title":"Proteins behaving badly: emerging technologies in profiling biopharmaceutical aggregation","volume":"31","author":"Hamrang","year":"2013","journal-title":"Trends Biotechnol."},{"key":"2019062808125162200_B4","article-title":"Advances in the prediction of protein aggregation propensity","author":"Pallares","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"2019062808125162200_B5","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev-chembioeng-060816-101404","article-title":"Driving forces for nonnative protein aggregation and approaches to predict Aggregation-Prone regions","volume":"8","author":"Meric","year":"2017","journal-title":"Annu. Rev. Chem. Biomol. Eng."},{"key":"2019062808125162200_B6","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/978-94-024-1069-3_7","volume-title":"From Protein Structure to Function with Bioinformatics","author":"Ricardo\u00a0Gra\u00f1a-Montes","year":"2017"},{"key":"2019062808125162200_B7","doi-asserted-by":"crossref","first-page":"W306","DOI":"10.1093\/nar\/gkv359","article-title":"AGGRESCAN3D (A3D): server for prediction of aggregation properties of protein structures","volume":"43","author":"Zambrano","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2019062808125162200_B8","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/978-1-4939-7756-7_21","article-title":"AGGRESCAN3D: Toward the prediction of the aggregation propensities of protein structures","volume":"1762","author":"Pujols","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"2019062808125162200_B9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1471-2105-8-65","article-title":"AGGRESCAN: a server for the prediction and evaluation of \u201chot spots\u201d of aggregation in polypeptides","volume":"8","author":"Conchillo-Sole","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"2019062808125162200_B10","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/978-1-61779-465-0_14","article-title":"AGGRESCAN: method, application, and perspectives for drug design","volume":"819","author":"de\u00a0Groot","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"2019062808125162200_B11","doi-asserted-by":"crossref","first-page":"W427","DOI":"10.1093\/nar\/gkt332","article-title":"CABS-flex: server for fast simulation of protein structure fluctuations","volume":"41","author":"Jamroz","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2019062808125162200_B12","doi-asserted-by":"crossref","first-page":"W338","DOI":"10.1093\/nar\/gky356","article-title":"CABS-flex 2.0: a web server for fast simulations of flexibility of protein structures","volume":"46","author":"Kuriata","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2019062808125162200_B13","doi-asserted-by":"crossref","first-page":"e1005824","DOI":"10.1371\/journal.pgen.1005824","article-title":"Specific Hsp100 chaperones determine the fate of the first enzyme of the plastidial isoprenoid pathway for either refolding or degradation by the stromal Clp protease in arabidopsis","volume":"12","author":"Pulido","year":"2016","journal-title":"PLos Genet."},{"key":"2019062808125162200_B14","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3390\/ijms17040552","article-title":"Insights into the antimicrobial mechanism of action of human RNase6: structural determinants for bacterial cell agglutination and membrane permeation","volume":"17","author":"Pulido","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"2019062808125162200_B15","doi-asserted-by":"crossref","first-page":"34869","DOI":"10.1038\/srep34869","article-title":"Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies","volume":"6","author":"Soler","year":"2016","journal-title":"Sci. Rep."},{"key":"2019062808125162200_B16","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1080\/07391102.2017.1310670","article-title":"The proteinopathy of D169G and K263E mutants at the RNA Recognition Motif (RRM) domain of tar DNA-binding protein (tdp43) causing neurological disorders: a computational study","volume":"36","author":"Bhandare","year":"2018","journal-title":"J. Biomol. Struct. Dyn."},{"key":"2019062808125162200_B17","doi-asserted-by":"crossref","first-page":"e2562","DOI":"10.1002\/jmr.2562","article-title":"Putative alternative functions of human stefin B (cystatin B): binding to amyloid-beta, membranes, and copper","volume":"30","author":"Zerovnik","year":"2017","journal-title":"J. Mol. Recognit."},{"key":"2019062808125162200_B18","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.bpj.2017.07.011","article-title":"sw ApoMb amyloid aggregation under nondenaturing conditions: the role of native structure stability","volume":"113","author":"Katina","year":"2017","journal-title":"Biophys. J."},{"key":"2019062808125162200_B19","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1021\/acs.molpharmaceut.8b00341","article-title":"Combining structural aggregation propensity and stability predictions to re-design protein solubility","volume":"15","author":"Gil-Garcia","year":"2018","journal-title":"Mol. Pharm."},{"key":"2019062808125162200_B20","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.xphs.2016.02.010","article-title":"Engineering a cysteine-free form of human fibroblast growth Factor-1 for \u201cSecond Generation\u201d therapeutic application","volume":"105","author":"Xia","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"2019062808125162200_B21","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1093\/bioinformatics\/bty685","article-title":"CABS-flex standalone: a simulation environment for fast modeling of protein flexibility","volume":"35","author":"Kurcinski","year":"2019","journal-title":"Bioinformatics"},{"key":"2019062808125162200_B22","doi-asserted-by":"crossref","first-page":"W382","DOI":"10.1093\/nar\/gki387","article-title":"The FoldX web server: an online force field","volume":"33","author":"Schymkowitz","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2019062808125162200_B23","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1093\/bioinformatics\/btu184","article-title":"CABS-flex predictions of protein flexibility compared with NMR ensembles","volume":"30","author":"Jamroz","year":"2014","journal-title":"Bioinformatics"},{"key":"2019062808125162200_B24","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1021\/ct300854w","article-title":"Consistent view of protein fluctuations from all-atom molecular dynamics and coarse-grained dynamics with knowledge-based force-field","volume":"9","author":"Jamroz","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"2019062808125162200_B25","doi-asserted-by":"crossref","first-page":"e183486","DOI":"10.1001\/jamaoncol.2018.3486","article-title":"Safety and efficacy of bevacizumab plus Standard-of-Care treatment beyond disease progression in patients with advanced non-small cell lung cancer: the AvaALL randomized clinical trial","volume":"4","author":"Gridelli","year":"2018","journal-title":"JAMA Oncol."},{"key":"2019062808125162200_B26","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.chroma.2014.04.027","article-title":"Capability measurement of size-exclusion chromatography with a light-scattering detection method in a stability study of bevacizumab using the process capability indices","volume":"1353","author":"Oliva","year":"2014","journal-title":"J. Chromatogr. A."},{"key":"2019062808125162200_B27","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/19420862.2015.1112477","article-title":"Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab","volume":"8","author":"Courtois","year":"2016","journal-title":"mAbs"},{"key":"2019062808125162200_B28","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.jmb.2008.03.020","article-title":"The in vivo and in vitro aggregation properties of globular proteins correlate with their conformational stability: the SH3 case","volume":"378","author":"Espargaro","year":"2008","journal-title":"J. Mol. Biol."},{"key":"2019062808125162200_B29","doi-asserted-by":"crossref","first-page":"4172","DOI":"10.1002\/pmic.201000260","article-title":"Deciphering the role of the thermodynamic and kinetic stabilities of SH3 domains on their aggregation inside bacteria","volume":"10","author":"Castillo","year":"2010","journal-title":"Proteomics"},{"key":"2019062808125162200_B30","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1093\/molbev\/msp146","article-title":"Structural determinants of protein evolution are context-sensitive at the residue level","volume":"26","author":"Franzosa","year":"2009","journal-title":"Mol. Biol. Evol."},{"key":"2019062808125162200_B31","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/S0958-1669(00)00152-X","article-title":"Phage display in pharmaceutical biotechnology","volume":"11","author":"Sidhu","year":"2000","journal-title":"Curr. Opin. Biotechnol."},{"key":"2019062808125162200_B32","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.jmb.2014.09.026","article-title":"The CamSol method of rational design of protein mutants with enhanced solubility","volume":"427","author":"Sormanni","year":"2015","journal-title":"J. Mol. Biol."},{"key":"2019062808125162200_B33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/protein\/gzt058","article-title":"Optimal charged mutations in the complementarity-determining regions that prevent domain antibody aggregation are dependent on the antibody scaffold","volume":"27","author":"Perchiacca","year":"2014","journal-title":"Protein Eng. Des. Sel."},{"key":"2019062808125162200_B34","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1080\/19420862.2016.1190060","article-title":"Structural diversity in a human antibody germline library","volume":"8","author":"Teplyakov","year":"2016","journal-title":"mAbs"},{"key":"2019062808125162200_B35","doi-asserted-by":"crossref","first-page":"10879","DOI":"10.1073\/pnas.1202866109","article-title":"General strategy for the generation of human antibody variable domains with increased aggregation resistance","volume":"109","author":"Dudgeon","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2019062808125162200_B36","doi-asserted-by":"crossref","first-page":"189","DOI":"10.12688\/f1000research.7931.1","article-title":"FreeSASA: an open source C library for solvent accessible surface area calculations [version 1; peer review: 2 approved]","volume":"5","author":"Mitternacht","year":"2016","journal-title":"F1000Research"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/advance-article-pdf\/doi\/10.1093\/nar\/gkz321\/28554633\/gkz321.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/47\/W1\/W300\/28879893\/gkz321.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,22]],"date-time":"2019-09-22T07:38:34Z","timestamp":1569137914000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/47\/W1\/W300\/5485072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,3]]},"references-count":36,"journal-issue":{"issue":"W1","published-online":{"date-parts":[[2019,5,3]]},"published-print":{"date-parts":[[2019,7,2]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkz321","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7,2]]},"published":{"date-parts":[[2019,5,3]]}}}