{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T02:18:26Z","timestamp":1772590706256,"version":"3.50.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","funder":[{"DOI":"10.13039\/501100009559","name":"Universidad Nacional de Quilmes","doi-asserted-by":"crossref","award":["1402\/15"],"award-info":[{"award-number":["1402\/15"]}],"id":[{"id":"10.13039\/501100009559","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2013-0232"],"award-info":[{"award-number":["PICT 2013-0232"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s12859-018-2044-2","type":"journal-article","created":{"date-parts":[[2018,1,30]],"date-time":"2018-01-30T13:34:22Z","timestamp":1517319262000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Large scale analysis of protein conformational transitions from aqueous to non-aqueous media"],"prefix":"10.1186","volume":"19","author":[{"given":"Ana Julia Velez","family":"Rueda","sequence":"first","affiliation":[]},{"given":"Alexander Miguel","family":"Monzon","sequence":"additional","affiliation":[]},{"given":"Sebasti\u00e1n M.","family":"Ardanaz","sequence":"additional","affiliation":[]},{"given":"Luis E.","family":"Iglesias","sequence":"additional","affiliation":[]},{"given":"Gustavo","family":"Parisi","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2018,1,30]]},"reference":[{"key":"2044_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/9783527621729","volume-title":"Organic synthesis with enzymes in non-aqueous media","author":"G Carrea","year":"2008","unstructured":"Carrea G, Riva S. Organic synthesis with enzymes in non-aqueous media. 2008;"},{"key":"2044_CR2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/35051719","volume":"409","author":"A Klibanov","year":"2001","unstructured":"Klibanov A. Improving enzymes by using them in organic solvents. Nature. 2001;409:241\u20136.","journal-title":"Nature"},{"key":"2044_CR3","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.tibtech.2007.10.007","volume":"26","author":"AL Serdakowski","year":"2008","unstructured":"Serdakowski AL, Dordick JS. Enzyme activation for organic solvents made easy. Trends Biotechnol. 2008;26:48\u201354.","journal-title":"Trends Biotechnol"},{"key":"2044_CR4","doi-asserted-by":"publisher","first-page":"10062","DOI":"10.1073\/pnas.96.18.10062","volume":"96","author":"XG Gao","year":"1999","unstructured":"Gao XG, Maldonado E, P\u00e9rez-Montfort R, et al. Crystal structure of triosephosphate isomerase from Trypanosoma cruzi in hexane. Proc Natl Acad Sci U S A. 1999;96:10062\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2044_CR5","doi-asserted-by":"publisher","first-page":"7326","DOI":"10.1021\/bi00189a038","volume":"33","author":"NH Yennawar","year":"1994","unstructured":"Yennawar NH, Yennawar HP, Farber GK. X-ray crystal structure of gamma-chymotrypsin in hexane. Biochemistry. 1994;33:7326\u201336.","journal-title":"Biochemistry"},{"key":"2044_CR6","doi-asserted-by":"publisher","first-page":"4250","DOI":"10.1073\/pnas.94.9.4250","volume":"94","author":"JL Schmitke","year":"1997","unstructured":"Schmitke JL, Stern LJ, Klibanov AM. The crystal structure of subtilisin Carlsberg in anhydrous dioxane and its comparison with those in water and acetonitrile. Proc Natl Acad Sci U S A. 1997;94:4250\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2044_CR7","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/S0167-4838(98)00226-X","volume":"1429","author":"G Zhu","year":"1998","unstructured":"Zhu G, Huang Q, Wang Z, et al. X-ray studies on two forms of bovine beta-trypsin crystals in neat cyclohexane. Biochim Biophys Acta. 1998;1429:142\u201350.","journal-title":"Biochim Biophys Acta"},{"key":"2044_CR8","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1107\/S0907444905009364","volume":"61","author":"A Deshpande","year":"2005","unstructured":"Deshpande A, Nimsadkar S, Mande SC. Effect of alcohols on protein hydration: crystallographic analysis of hen egg-white lysozyme in the presence of alcohols. Acta Crystallogr Sect D Biol Crystallogr. 2005;61:1005\u20138.","journal-title":"Acta Crystallogr Sect D Biol Crystallogr"},{"key":"2044_CR9","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1002\/(SICI)1097-0134(19991201)37:4<628::AID-PROT13>3.0.CO;2-G","volume":"37","author":"AC English","year":"1999","unstructured":"English AC, Done SH, Caves LS, et al. Locating interaction sites on proteins: the crystal structure of thermolysin soaked in 2% to 100% isopropanol. Proteins. 1999;37:628\u201340.","journal-title":"Proteins"},{"key":"2044_CR10","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1002\/(SICI)1097-0290(19980320)57:6<746::AID-BIT12>3.0.CO;2-5","volume":"57","author":"T Ke","year":"1998","unstructured":"Ke T, Klibanov AM. On enzymatic activity in organic solvents as a function of enzyme history. Biotechnol Bioeng. 1998;57:746\u201350.","journal-title":"Biotechnol Bioeng"},{"key":"2044_CR11","first-page":"310","volume":"29","author":"J Saraiva","year":"1996","unstructured":"Saraiva J, Oliveira J, Hendrickx M. Thermal inactivation kinetics of. Food Sci Technol. 1996;29:310\u20135.","journal-title":"Food Sci Technol"},{"key":"2044_CR12","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1021\/ja9935198","volume":"122","author":"MT Ru","year":"2000","unstructured":"Ru MT, Hirokane SY, Lo AS, et al. On the salt-induced activation of lyophilized enzymes in organic solvents: effect of salt kosmotropicity on enzyme activity. J Am Chem Soc. 2000;122:1565\u201371.","journal-title":"J Am Chem Soc"},{"key":"2044_CR13","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/0968-0004(89)90146-1","volume":"14","author":"AM Klibanov","year":"1989","unstructured":"Klibanov AM. Enzymatic catalysis in anhydrous organic solvents. Trends Biochem Sci. 1989;14:141\u20134.","journal-title":"Trends Biochem Sci"},{"key":"2044_CR14","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1098\/rstb.2004.1506","volume":"359","author":"DS Clark","year":"2004","unstructured":"Clark DS. Characteristics of nearly dry enzymes in organic solvents: implications for biocatalysis in the absence of water. Philos Trans R Soc Lond Ser B Biol Sci. 2004;359:1299\u2013307. 1323\u20131328","journal-title":"Philos Trans R Soc Lond Ser B Biol Sci"},{"key":"2044_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.tibs.2013.11.001","volume":"39","author":"M Elias","year":"2014","unstructured":"Elias M, Wieczorek G, Rosenne S, et al. The universality of enzymatic rate-temperature dependency. Trends Biochem Sci. 2014;39:1\u20137.","journal-title":"Trends Biochem Sci"},{"key":"2044_CR16","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1110\/ps.9.1.10","volume":"9","author":"S Kumar","year":"2000","unstructured":"Kumar S, Ma B, Tsai CJ, et al. Folding and binding cascades: dynamic landscapes and population shifts. Protein Sci. 2000;9:10\u20139.","journal-title":"Protein Sci"},{"key":"2044_CR17","doi-asserted-by":"publisher","first-page":"6739","DOI":"10.1021\/bi00188a001","volume":"33","author":"M Gerstein","year":"1994","unstructured":"Gerstein M, Lesk AM, Chothia C. Structural mechanisms for domain movements in proteins. Biochemistry. 1994;33:6739\u201349.","journal-title":"Biochemistry"},{"key":"2044_CR18","doi-asserted-by":"publisher","first-page":"4280","DOI":"10.1093\/nar\/26.18.4280","volume":"26","author":"M Gerstein","year":"1998","unstructured":"Gerstein M, Krebs W. A database of macromolecular motions. Nucleic Acids Res. 1998;26:4280\u201390.","journal-title":"Nucleic Acids Res"},{"key":"2044_CR19","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1021\/ct501085y","volume":"11","author":"Y Gu","year":"2015","unstructured":"Gu Y, Li D-W, Br\u00fcschweiler R. Decoding the mobility and time scales of protein loops. J Chem Theory Comput. 2015;11:1308\u201314.","journal-title":"J Chem Theory Comput"},{"key":"2044_CR20","doi-asserted-by":"publisher","first-page":"6589","DOI":"10.1021\/cr400525m","volume":"114","author":"R van der Lee","year":"2014","unstructured":"van der Lee R, Buljan M, Lang B, et al. Classification of intrinsically disordered regions and proteins. Chem Rev. 2014;114:6589\u2013631.","journal-title":"Chem Rev"},{"key":"2044_CR21","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1038\/2605","volume":"4","author":"DE Koshland","year":"1998","unstructured":"Koshland DE. Conformational changes: how small is big enough? Nat Med. 1998;4:1112\u20134.","journal-title":"Nat Med"},{"key":"2044_CR22","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1126\/science.277.5323.202","volume":"277","author":"AD Mesecar","year":"1997","unstructured":"Mesecar AD, Stoddard BL, Koshland DE Jr. Orbital steering in the catalytic power of enzymes\u00a0: small structural changes with large catalytic consequences. Science. 1997;277:202\u20136. (80-. )","journal-title":"Science"},{"key":"2044_CR23","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jmb.2004.11.013","volume":"346","author":"A Gutteridge","year":"2005","unstructured":"Gutteridge A, Thornton J. Conformational changes observed in enzyme crystal structures upon substrate binding. J Mol Biol. 2005;346:21\u20138.","journal-title":"J Mol Biol"},{"key":"2044_CR24","doi-asserted-by":"publisher","first-page":"5871","DOI":"10.1021\/cr300384w","volume":"113","author":"A Gora","year":"2013","unstructured":"Gora A, Brezovsky J, Damborsky J. Gates of enzymes. Chem Rev. 2013;113:5871\u2013923.","journal-title":"Chem Rev"},{"key":"2044_CR25","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1371\/journal.pcbi.1002708","volume":"8","author":"E Chovancova","year":"2012","unstructured":"Chovancova E, Pavelka A, Benes P, et al. CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures. PLoS Comput Biol. 2012;8:23\u201330.","journal-title":"PLoS Comput Biol"},{"key":"2044_CR26","doi-asserted-by":"publisher","unstructured":"Monzon AM, Rohr CO, Fornasari MS, et al. CoDNaS 2.0: a comprehensive database of protein conformational diversity in the native state. Database. 2016;2016. baw038. https:\/\/doi.org\/10.1093\/database\/baw038 .","DOI":"10.1093\/database\/baw038"},{"key":"2044_CR27","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1002\/pro.2931","volume":"25","author":"D Zea","year":"2016","unstructured":"Zea D, Monzon AM, Gonzalez C, et al. Disorder transitions and conformational diversity cooperatively modulate biological function in proteins. Protein Sci. 2016;25:1138\u201346.","journal-title":"Protein Sci"},{"key":"2044_CR28","doi-asserted-by":"publisher","first-page":"10505","DOI":"10.1073\/pnas.0812152106","volume":"106","author":"PV Burra","year":"2009","unstructured":"Burra PV, Zhang Y, Godzik A, et al. Global distribution of conformational states derived from redundant models in the PDB points to non-uniqueness of the protein structure. Proc Natl Acad Sci U S A. 2009;106:10505\u201310.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2044_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pcbi.1005398","volume":"13","author":"AM Monzon","year":"2017","unstructured":"Monzon AM, Zea DJ, Fornasari MS, et al. Conformational diversity analysis reveals three functional mechanisms in proteins. PLoS Comput Biol. 2017;13:1\u201329.","journal-title":"PLoS Comput Biol"},{"key":"2044_CR30","doi-asserted-by":"publisher","first-page":"D129","DOI":"10.1093\/nar\/gkh028","volume":"32","author":"CT Porter","year":"2004","unstructured":"Porter CT, Bartlett GJ, Thornton JM. The catalytic site atlas: a resource of catalytic sites and residues identified in enzymes using structural data. Nucleic Acids Res. 2004;32:D129\u201333.","journal-title":"Nucleic Acids Res"},{"key":"2044_CR31","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/348125a0","volume":"348","author":"HR Bourne","year":"1990","unstructured":"Bourne HR, Sanders DA, McCormick F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature. 1990;348:125\u201332.","journal-title":"Nature"},{"key":"2044_CR32","doi-asserted-by":"publisher","first-page":"22696","DOI":"10.1074\/jbc.M110.125161","volume":"285","author":"F Shima","year":"2010","unstructured":"Shima F, Ijiri Y, Liao J, et al. Structural basis for conformational dynamics of GTP-bound. J Biol Chem. 2010;285:22696\u2013705.","journal-title":"J Biol Chem"},{"key":"2044_CR33","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/S0969-2126(03)00128-X","volume":"11","author":"G Buhrman","year":"2003","unstructured":"Buhrman G, De Serrano V, Mattos C, et al. Organic solvents order the dynamic switch II in Ras crystals. Structure. 2003;11:747\u201351.","journal-title":"Structure"},{"key":"2044_CR34","doi-asserted-by":"publisher","first-page":"5706","DOI":"10.1073\/pnas.0601113103","volume":"103","author":"RK Eppler","year":"2006","unstructured":"Eppler RK, Komor RS, Huynh J, et al. Water dynamics and salt-activation of enzymes in organic media: mechanistic implications revealed by NMR spectroscopy. Proc Natl Acad Sci U S A. 2006;103:5706\u201310.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2044_CR35","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acids Res. 2000;28:235\u201342.","journal-title":"Nucleic Acids Res"},{"key":"2044_CR36","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/S0959-440X(01)00278-0","volume":"11","author":"C Mattos","year":"2001","unstructured":"Mattos C, Ringe D. Proteins in organic solvents. Curr Opin Struct Biol. 2001;11:761\u20134.","journal-title":"Curr Opin Struct Biol"},{"key":"2044_CR37","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1002\/pro.5560070905","volume":"7","author":"J Liang","year":"1998","unstructured":"Liang J, Edelsbrunner H, Woodward C. Anatomy of protein pockets and cavities: measurement of binding site geometry and implications for ligand design. Protein Sci. 1998;7:1884\u201397.","journal-title":"Protein Sci"},{"key":"2044_CR38","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1002\/pro.125","volume":"18","author":"BW Matthews","year":"2009","unstructured":"Matthews BW, Liu L. A review about nothing: are apolar cavities in proteins really empty? Protein Sci. 2009;18:494\u2013502.","journal-title":"Protein Sci"},{"key":"2044_CR39","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1002\/cbic.201200733","volume":"14","author":"V Stepankova","year":"2013","unstructured":"Stepankova V, Khabiri M, Brezovsky J, et al. Expansion of access tunnels and active-site cavities influence activity of haloalkane dehalogenases in organic cosolvents. Chembiochem. 2013;14:890\u20137.","journal-title":"Chembiochem"},{"key":"2044_CR40","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1021\/ar5002928","volume":"48","author":"R Callender","year":"2015","unstructured":"Callender R, Dyer RB. The dynamical nature of enzymatic catalysis. Acc Chem Res. 2015;48:407\u201313.","journal-title":"Acc Chem Res"},{"key":"2044_CR41","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jmgm.2014.10.011","volume":"55","author":"N Desdouits","year":"2015","unstructured":"Desdouits N, Nilges M, Blondel A. Principal component analysis reveals correlation of cavities evolution and functional motions in proteins. J Mol Graph Model. 2015;55:13\u201324.","journal-title":"J Mol Graph Model"},{"key":"2044_CR42","doi-asserted-by":"publisher","first-page":"D1096","DOI":"10.1093\/nar\/gks966","volume":"41","author":"J Yang","year":"2013","unstructured":"Yang J, Roy A, Zhang Y. BioLiP: a semi-manually curated database for biologically relevant ligand-protein interactions. Nucleic Acids Res. 2013;41:D1096\u2013103.","journal-title":"Nucleic Acids Res"},{"key":"2044_CR43","first-page":"2606","volume-title":"MAMMOTH ( Matching molecular models obtained from theory ): an automated method for model comparison","author":"AR Ortiz","year":"2002","unstructured":"Ortiz AR, Strauss CEM. MAMMOTH ( Matching molecular models obtained from theory ): an automated method for model comparison; 2002. p. 2606\u201321."},{"key":"2044_CR44","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, et al. A series of PDB-related databanks for everyday needs. Nucleic Acids Res. 2015;43:D364\u20138.","journal-title":"Nucleic Acids Res"},{"key":"2044_CR45","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/S0968-0004(02)02169-2","volume":"27","author":"P Tompa","year":"2002","unstructured":"Tompa P. Intrinsically unstructured proteins. Trends Biochem Sci. 2002;27:527\u201333.","journal-title":"Trends Biochem Sci"},{"key":"2044_CR46","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/0471721204.ch13","volume":"44","author":"CA Orengo","year":"2003","unstructured":"Orengo CA, Pearl FM, Thornton JM. The CATH domain structure database. Methods Biochem Anal. 2003;44:249\u201371.","journal-title":"Methods Biochem Anal"},{"key":"2044_CR47","doi-asserted-by":"publisher","first-page":"3125","DOI":"10.1039\/C3CC46135A","volume":"50","author":"RM Bullock","year":"2014","unstructured":"Bullock RM, Appel AM, Helm ML. Production of hydrogen by electrocatalysis: making the H\u2013H bond by combining protons and hydrides. Chem Commun. 2014;50:3125\u201343.","journal-title":"Chem Commun"},{"key":"2044_CR48","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/1471-2105-10-168","volume":"10","author":"V Le Guilloux","year":"2009","unstructured":"Le Guilloux V, Schmidtke P, Tuffery P. Fpocket: an open source platform for ligand pocket detection. BMC Bioinformatics. 2009;10:168.","journal-title":"BMC Bioinformatics"},{"key":"2044_CR49","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1758-2946-5-39","volume":"5","author":"D Sehnal","year":"2013","unstructured":"Sehnal D, Svobodov\u00e1 Va Ekov\u00e1 R, Berka K, et al. MOLE 2.0: advanced approach for analysis of biomacromolecular channels. J Cheminform. 2013;5:39.","journal-title":"J Cheminform"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-018-2044-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T19:11:51Z","timestamp":1693509111000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-018-2044-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,30]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["2044"],"URL":"https:\/\/doi.org\/10.1186\/s12859-018-2044-2","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,30]]},"assertion":[{"value":"29 August 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2018","order":3,"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":"27"}}