{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T01:26:49Z","timestamp":1768094809600,"version":"3.49.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"crossref","award":["2016YFA0502301"],"award-info":[{"award-number":["2016YFA0502301"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872797"],"award-info":[{"award-number":["81872797"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science & Technology Major Project \u201cKey New Drug Creation and Manufacturing Program\u201d","award":["2018ZX09711002"],"award-info":[{"award-number":["2018ZX09711002"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Knowledge of protein motions is significant to understand its functions. While currently available databases for protein motions are mostly focused on overall domain motions, little attention is paid on local residue motions. Albeit with relatively small scale, the local residue motions, especially those residues in binding pockets, may play crucial roles in protein functioning and ligands binding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A comprehensive protein motion database, namely D3PM, was constructed in this study to facilitate the analysis of protein motions. The protein motions in the D3PM range from overall structural changes of macromolecule to local flip motions of binding pocket residues. Currently, the D3PM has collected 7679 proteins with overall motions and 3513 proteins with pocket residue motions. The motion patterns are classified into 4 types of overall structural changes and 5 types of pocket residue motions. Impressively, we found that less than 15% of protein pairs have obvious overall conformational adaptations induced by ligand binding, while more than 50% of protein pairs have significant structural changes in ligand binding sites, indicating that ligand-induced conformational changes are drastic and mainly confined around ligand binding sites. Based on the residue preference in binding pocket, we classified amino acids into \u201cpocketphilic\u201d and \u201cpocketphobic\u201d residues, which should be helpful for pocket prediction and drug design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>D3PM is a comprehensive database about protein motions ranging from residue to domain, which should be useful for exploring diverse protein motions and for understanding protein function and drug design. The D3PM is available on<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.d3pharma.com\/D3PM\/index.php\">www.d3pharma.com\/D3PM\/index.php<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12859-022-04595-0","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T13:03:11Z","timestamp":1644843791000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["D3PM: a comprehensive database for protein motions ranging from residue to domain"],"prefix":"10.1186","volume":"23","author":[{"given":"Cheng","family":"Peng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinben","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoqiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6699-5299","authenticated-orcid":false,"given":"Weiliang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"4595_CR1","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/nsb0902-646","volume":"9","author":"M Karplus","year":"2002","unstructured":"Karplus M, McCammon JA. Molecular dynamics simulations of biomolecules. Nat Struct Mol Biol. 2002;9:646\u201352.","journal-title":"Nat Struct Mol Biol"},{"key":"4595_CR2","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0959-440X(00)00061-0","volume":"10","author":"HJC Berendsen","year":"2000","unstructured":"Berendsen HJC. Collective protein dynamics in relation to function. Curr Opin Struct Biol. 2000;10:165\u20139.","journal-title":"Curr Opin Struct Biol"},{"key":"4595_CR3","doi-asserted-by":"publisher","first-page":"323","DOI":"10.2174\/1381612053382106","volume":"11","author":"M Venkatraman","year":"2005","unstructured":"Venkatraman M, Alan CG, Maxwell DC, et al. Docking: successes and challenges. Curr Pharm Des. 2005;11:323\u201333.","journal-title":"Curr Pharm Des"},{"key":"4595_CR4","doi-asserted-by":"publisher","first-page":"3016","DOI":"10.3390\/ijms11083016","volume":"11","author":"SY Huang","year":"2010","unstructured":"Huang SY, Zou X. Advances and challenges in protein-ligand docking. Int J Mol Sci. 2010;11:3016\u201334.","journal-title":"Int J Mol Sci"},{"key":"4595_CR5","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1103\/RevModPhys.73.17","volume":"73","author":"A Rousse","year":"2001","unstructured":"Rousse A, Rischel C, Gauthier JC. Colloquium: femtosecond X-ray crystallography. Rev Mod Phys. 2001;73:17\u201331.","journal-title":"Rev Mod Phys"},{"key":"4595_CR6","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3109\/10409238409117796","volume":"15","author":"WS Bennett","year":"2008","unstructured":"Bennett WS, Huber R, Engel J. Structural and functional aspects of domain motions in proteins. Crit Rev Biochem. 2008;15:291\u2013384.","journal-title":"Crit Rev Biochem"},{"key":"4595_CR7","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.theochem.2008.09.024","volume":"898","author":"L Skjaerven","year":"2009","unstructured":"Skjaerven L, Hollup SM, Reuter N. Normal mode analysis for proteins. J Mol Struct. 2009;898:42\u20138.","journal-title":"J Mol Struct"},{"key":"4595_CR8","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3109\/10409238109105437","volume":"9","author":"M Karplus","year":"1981","unstructured":"Karplus M, McCammon JA. The internal dynamics of globular protein. Crit Rev Biochem. 1981;9:293\u2013349.","journal-title":"Crit Rev Biochem"},{"key":"4595_CR9","doi-asserted-by":"publisher","first-page":"141","DOI":"10.3109\/10409237509102555","volume":"3","author":"G Careri","year":"1975","unstructured":"Careri G, Fasella P. Statistical time events in enzymes: a physical assessmen. Crit Rev Biochem. 1975;3:141\u201364.","journal-title":"Crit Rev Biochem"},{"key":"4595_CR10","first-page":"73","volume":"33","author":"FRN Gurd","year":"1979","unstructured":"Gurd FRN, Rothgeb M. Motions in proteins. Adv Prot Chem. 1979;33:73\u2013165.","journal-title":"Adv Prot Chem"},{"key":"4595_CR11","first-page":"473","volume":"66","author":"A Cooper","year":"1980","unstructured":"Cooper A. Conformational fluctuation and change in biological macromolecules. Sci Prog. 1980;66:473\u201397.","journal-title":"Sci Prog"},{"key":"4595_CR12","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1002\/(SICI)1097-0134(19990215)34:3<369::AID-PROT9>3.0.CO;2-F","volume":"34","author":"H Konrad","year":"1999","unstructured":"Konrad H, Aline T, Field MJ. Analysis of domain motions in large proteins. Proteins. 1999;34:369\u201382.","journal-title":"Proteins"},{"key":"4595_CR13","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1006\/jmbi.1993.1592","volume":"234","author":"M Gerstein","year":"1993","unstructured":"Gerstein M, Anderson BF, Norris GE, et al. Domain closure in lactoferrin. J Mol Biol. 1993;234:357\u201372.","journal-title":"J Mol Biol"},{"key":"4595_CR14","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. Biochem. 1994;33:6739\u201349.","journal-title":"Biochem"},{"key":"4595_CR15","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1143\/JPSJ.32.1331","volume":"32","author":"K Nishikawa","year":"1972","unstructured":"Nishikawa K, Ooi T, Isogai Y, et al. Representation and computation of the conformations. J Phys Soc Jpn. 1972;32:1331\u20137.","journal-title":"J Phys Soc Jpn"},{"key":"4595_CR16","doi-asserted-by":"publisher","first-page":"2832","DOI":"10.1093\/bioinformatics\/bti420","volume":"21","author":"G Qi","year":"2005","unstructured":"Qi G, Lee R, Hayward SA. Comprehensive and non-redundant database of protein domain movements. Bioinformatics. 2005;21:2832\u20138.","journal-title":"Bioinformatics"},{"key":"4595_CR17","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1093\/nar\/gkg104","volume":"31","author":"N Echols","year":"2003","unstructured":"Echols N. MolMovDB: analysis and visualization of conformational change and structural flexibility. Nucleic Acids Res. 2003;31:478\u201382.","journal-title":"Nucleic Acids Res"},{"key":"4595_CR18","doi-asserted-by":"publisher","first-page":"D471","DOI":"10.1093\/nar\/gkx1071","volume":"46","author":"D Piovesan","year":"2018","unstructured":"Piovesan D, Tabaro F, Paladin L, et al. MobiDB 3.0: more annotations for intrinsic disorder, conformational diversity and interactions in proteins. Nucleic Acids Res. 2018;46:D471\u20136.","journal-title":"Nucleic Acids Res"},{"key":"4595_CR19","doi-asserted-by":"publisher","first-page":"D296","DOI":"10.1093\/nar\/gkj046","volume":"34","author":"S Flores","year":"2006","unstructured":"Flores S, Echols N, Milburn D, et al. The Database of Macromolecular Motions: new features added at the decade mark. Nucleic Acids Res. 2006;34:D296-301.","journal-title":"Nucleic Acids Res"},{"key":"4595_CR20","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1073\/pnas.72.6.2002","volume":"72","author":"BR Gelin","year":"1975","unstructured":"Gelin BR. Sidechain torsional potentials and motion of amino acids in proteins: bovine pancreatic trypsin inhibito. Proc Natl Acad Sci U S A. 1975;72:2002\u20136.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4595_CR21","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":"4595_CR22","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1042\/bj3390371","volume":"339","author":"MA Noble","year":"1999","unstructured":"Noble MA, Miles CS, Chapman SK, et al. Roles of key active-site residues in flavocytochrome P450 BM3. Biochem J. 1999;339:371\u20139.","journal-title":"Biochem J"},{"key":"4595_CR23","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1016\/j.bcp.2004.08.013","volume":"68","author":"PH Keizers","year":"2004","unstructured":"Keizers PH, Lussenburg BM, de Graaf C, et al. Influence of phenylalanine 120 on cytochrome P450 2D6 catalytic selectivity and regiospecificity: crucial role in 7-methoxy-4-(aminomethyl)-coumarin metabolism. Biochem Pharmacol. 2004;68:2263\u201371.","journal-title":"Biochem Pharmacol"},{"key":"4595_CR24","doi-asserted-by":"publisher","first-page":"8284","DOI":"10.1073\/pnas.1306265110","volume":"110","author":"G Yongxia","year":"2013","unstructured":"Yongxia G, Zheng Z, James JLC, et al. Smoke-derived karrikin perception by the \u03b1\/\u03b2-hydrolase KAI2 from Arabidopsis. Proc Natl Acad Sci U S A. 2013;110:8284\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4595_CR25","doi-asserted-by":"publisher","first-page":"14075","DOI":"10.1021\/ja026811f","volume":"124","author":"Y Wang","year":"2002","unstructured":"Wang Y, Jardetzky O. Investigation of the neighboring residue effects on protein chemical shifts. J Am Chem Soc. 2002;124:14075\u201384.","journal-title":"J Am Chem Soc"},{"key":"4595_CR26","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1111\/j.1432-1033.1977.tb11885.x","volume":"80","author":"FC Bernstein","year":"1977","unstructured":"Bernstein FC, Koetzle TF, Williams GJB, et al. The protein data bank: a computer-based archival file for macromolecular structures. Eur J Biochem. 1977;80:319\u201324.","journal-title":"Eur J Biochem"},{"key":"4595_CR27","doi-asserted-by":"publisher","first-page":"D283","DOI":"10.1093\/nar\/gkp963","volume":"38","author":"MY Lobanov","year":"2010","unstructured":"Lobanov MY, Shoemaker BA, Garbuzynskiy SO, et al. ComSin: database of protein structures in bound (complex) and unbound (single) states in relation to their intrinsic disorder. Nucleic Acids Res. 2010;38:D283\u20137.","journal-title":"Nucleic Acids Res"},{"key":"4595_CR28","doi-asserted-by":"publisher","first-page":"D472","DOI":"10.1093\/nar\/gkr940","volume":"40","author":"DT Chang","year":"2012","unstructured":"Chang DT, Yao TJ, Fan CY, et al. AH-DB: collecting protein structure pairs before and after binding. Nucleic Acids Res. 2012;40:D472\u20138.","journal-title":"Nucleic Acids Res"},{"key":"4595_CR29","doi-asserted-by":"publisher","first-page":"D423","DOI":"10.1093\/nar\/gkv1316","volume":"44","author":"T Hrabe","year":"2016","unstructured":"Hrabe T, Li Z, Sedova M, et al. PDBFlex: exploring flexibility in protein structures. Nucleic Acids Res. 2016;44:D423\u20138.","journal-title":"Nucleic Acids Res"},{"key":"4595_CR30","doi-asserted-by":"publisher","first-page":"D554","DOI":"10.1093\/nar\/gkr966","volume":"40","author":"T Amemiya","year":"2012","unstructured":"Amemiya T, Koike R, Kidera A, et al. PSCDB: a database for protein structural change upon ligand binding. Nucleic Acids Res. 2012;40:D554\u20138.","journal-title":"Nucleic Acids Res"},{"key":"4595_CR31","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/nrd1129","volume":"2","author":"SJ Teague","year":"2003","unstructured":"Teague SJ. Implications of protein flexibility for drug discovery. Nat Rev Drug Discov. 2003;2:527\u201341.","journal-title":"Nat Rev Drug Discov"},{"key":"4595_CR32","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1126\/science.1169375","volume":"324","author":"N Tokuriki","year":"2009","unstructured":"Tokuriki N. Protein dynamism and evolvability. Science. 2009;324:203\u20137.","journal-title":"Science"},{"key":"4595_CR33","doi-asserted-by":"publisher","first-page":"D475","DOI":"10.1093\/nar\/gkq1181","volume":"39","author":"EI Juritz","year":"2011","unstructured":"Juritz EI, Alberti SF, Parisi GD. PCDB: a database of protein conformational diversity. Nucleic Acids Res. 2011;39:D475\u20139.","journal-title":"Nucleic Acids Res"},{"key":"4595_CR34","doi-asserted-by":"publisher","first-page":"baw038","DOI":"10.1093\/database\/baw038","volume":"2016","author":"AM Monzon","year":"2016","unstructured":"Monzon AM, Rohr CO, Fornasari MS, et al. CoDNaS 2.0: a comprehensive database of protein conformational diversity in the native state. Database (Oxford). 2016;2016:baw038.","journal-title":"Database (Oxford)"},{"key":"4595_CR35","doi-asserted-by":"publisher","first-page":"baw029","DOI":"10.1093\/database\/baw029","volume":"2016","author":"CW Chang","year":"2016","unstructured":"Chang CW, Chou CW, Chang DT. CCProf: exploring conformational change profile of proteins. Database (Oxford). 2016;2016:baw029.","journal-title":"Database (Oxford)"},{"key":"4595_CR36","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/prot.10119","volume":"47","author":"N Paul","year":"2002","unstructured":"Paul N, Rognan D. ConsDock: A new program for the consensus analysis of protein-ligand interactions. Proteins. 2002;47:521\u201333.","journal-title":"Proteins"},{"key":"4595_CR37","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31:455\u201361.","journal-title":"J Comput Chem"},{"key":"4595_CR38","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1021\/acs.accounts.5b00516","volume":"49","author":"A Stank","year":"2016","unstructured":"Stank A, Kokh DB, Fuller JC, et al. Protein Binding Pocket Dynamics. Acc Chem Res. 2016;49:809\u201315.","journal-title":"Acc Chem Res"},{"key":"4595_CR39","doi-asserted-by":"publisher","first-page":"18101","DOI":"10.1073\/pnas.0608849103","volume":"103","author":"MA Emrick","year":"2006","unstructured":"Emrick MA, Lee T, Starkey PJ, et al. The gatekeeper residue controls autoactivation of ERK2 via a pathway of intramolecular connectivity. Proc Natl Acad Sci U S A. 2006;103:18101\u20136.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4595_CR40","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1016\/j.str.2012.07.013","volume":"20","author":"G de Leon-Boenig","year":"2012","unstructured":"de Leon-Boenig G, Bowman KK, Feng JA, et al. The crystal structure of the catalytic domain of the NF-kappaB inducing kinase reveals a narrow but flexible active site. Structure. 2012;20:1704\u201314.","journal-title":"Structure"},{"key":"4595_CR41","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1128\/AAC.01887-15","volume":"60","author":"ST Lefurgy","year":"2016","unstructured":"Lefurgy ST, Malashkevich VN, Aguilan JT, et al. Analysis of the Structure and Function of FOX-4 Cephamycinase. Antimicrob Agents Chemother. 2016;60:717\u201328.","journal-title":"Antimicrob Agents Chemother"},{"key":"4595_CR42","doi-asserted-by":"publisher","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","volume":"46","author":"DS Wishart","year":"2018","unstructured":"Wishart DS, Feunang YD, Guo AC, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46:D1074\u201382.","journal-title":"Nucleic Acids Res"},{"key":"4595_CR43","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/bmb.2006.494034042644","volume":"34","author":"A Herraez","year":"2006","unstructured":"Herraez A. Biomolecules in the computer\u2014Jmol to the rescue. Biochem Mol Biol Educ. 2006;34:255\u201361.","journal-title":"Biochem Mol Biol Educ"},{"key":"4595_CR44","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1021\/ci5006004","volume":"55","author":"A Borrel","year":"2015","unstructured":"Borrel A, Regad L, Xhaard H, et al. PockDrug: a model for predicting pocket druggability that overcomes pocket estimation uncertainties. J Chem Inf Model. 2015;55:882\u201395.","journal-title":"J Chem Inf Model"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-022-04595-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-022-04595-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-022-04595-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T12:55:19Z","timestamp":1700225719000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-022-04595-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,14]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["4595"],"URL":"https:\/\/doi.org\/10.1186\/s12859-022-04595-0","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,14]]},"assertion":[{"value":"14 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}