{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:19:32Z","timestamp":1788434372776,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Bone morphogenetic protein\u20102 (BMP\u20102) is a key osteoinductive growth factor employed clinically in spinal fusion and fracture repair where bone regeneration is insufficient. However, its therapeutic efficacy is limited by low solubility and aggregation at physiological pH. This study investigates BMP\u20102 aggregation and identifies additives that stabilize its native, biologically active dimer form under physiological conditions. We demonstrate that 3\u2010[(3\u2010cholamidopropyl) dimethylammonio]\u20101\u2010propanesulfonate (CHAPS) efficiently refolded monomeric BMP\u20102 from inclusion bodies into dimeric form but failed to prevent aggregation of the folded dimer. In contrast, arginine did not promote refolding but significantly enhanced solubility and stability of the native dimer against aggregation as evidenced by turbidity, Rayleigh scattering, nanoparticle tracking analysis (NTA), dynamic light scattering (DLS) and microscopic analyzes. Functional assays, including alkaline phosphatase (ALP) activity, calcium deposition, and native PAGE, verified that BMP\u20102 retained its biological activity in presence of arginine. Tryptophan fluorescence and in silico analysis revealed distinct interaction mechanisms to BMP\u20102: CHAPS interacts with aromatic residues, enhancing flexibility and stabilizes open conformation, whereas arginine binds preferentially to acidic residues, promoting a compact, closed conformation. Collectively, arginine confers robust stabilization of BMP\u20102 at physiological pH, offering a rational framework for developing stable and therapeutically effective BMP\u20102 formulations.<\/jats:p>","DOI":"10.1002\/prot.70149","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:10:28Z","timestamp":1781064628000},"page":"1702-1716","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stabilization of Bone Morphogenetic Protein\u20102 at Physiological\n                    <scp>pH<\/scp>\n                    : Contrasting Roles of\n                    <scp>CHAPS<\/scp>\n                    and Arginine in Aggregation Inhibition"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7498-7659","authenticated-orcid":false,"given":"Hirah","family":"Amir","sequence":"first","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Delhi  Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baibhabshri","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Delhi  Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Gaur","sequence":"additional","affiliation":[{"name":"School of Interdisciplinary Research (SIRe) Indian Institute of Technology Delhi  Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-8205","authenticated-orcid":false,"given":"Shashank","family":"Deep","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Delhi  Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.150.3698.893"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.10.003"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2020.11.212"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2590"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2009.10.007"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2014.07.005"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.07.011"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2005001000003"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020903"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(200005)50:2<227::AID-JBM18>3.0.CO;2-2"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0295n.x"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.125123"},{"key":"e_1_2_13_14_1","first-page":"1","article-title":"Aggregation and Cellular Toxicity of Pathogenic or Non\u2010Pathogenic Proteins","volume":"10","author":"Lee S.","year":"2020","journal-title":"Scientific Reports"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2005.12.011"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2010.02.015"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010019\u20102705\u20105"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12121143"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2025.106662"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp111920y"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2017.04.013"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jct.2014.06.024"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2017.09.033"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp0498793"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi300942x"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.4c04901"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706029200"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct900549r"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp003020w"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.2408420"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.328693"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.477415"},{"key":"e_1_2_13_34_1","first-page":"7678","article-title":"How to Mesh Up Ewald sums. 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