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But apparently, not all types of NPs can serve as scaffolds for CE. To expedite the CE technology on a broader variety of NPs, the essential characteristic of NPs as scaffolds for CE needs to be identified. Herein, we investigate the potential of two distinct types of NPs as scaffolds for CE: CdSe\/ZnS quantum dots (QDs), an ionic compound NP, and palladium NPs (PdNPs), a metal NP. The results demonstrate that while QDs cannot support the restoration of the native conformation and function of the complementary\u2010determining region (CDR) fragments of antibodies, PdNPs can. The notably disparate outcomes unequivocally show that the mobility of the surface atoms\/adatoms of the NPs or the mobility of the conjugating bonds to the NPs is essential for CE, which allows the conjugated peptides to undergo a conformational change from their initial random conformation to their most stable native conformation under the constraints mimicking the native long\u2010range interactions in the original proteins. This discovery opens the door for CE on more NPs in the future.<\/jats:p>","DOI":"10.1002\/cmdc.202400832","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T22:35:36Z","timestamp":1736894136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Conformational Engineering of Flexible Protein Fragments on the Surface of Different Nanoparticles: The Surface\u2010Atom Mobility Rules"],"prefix":"10.1002","volume":"20","author":[{"given":"Wenxian","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Nanochemistry and Nanobiology Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Nanochemistry and Nanobiology Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiyu","family":"Che","sequence":"additional","affiliation":[{"name":"Institute of Nanochemistry and Nanobiology Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-2089","authenticated-orcid":false,"given":"Haifang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Nanochemistry and Nanobiology Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1168-3623","authenticated-orcid":false,"given":"Aoneng","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Nanochemistry and Nanobiology Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,26]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.03.020"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2016.14"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b09713"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-019-0592-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2024-0084"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1713526115"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202100623"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202300185"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.2c03200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","unstructured":"R. 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