{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:59:12Z","timestamp":1792159152392,"version":"4.4.0"},"reference-count":146,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hong Kong General Research Fund from the Research Grants Council of the Hong Kong Special Administrative Region, China","award":["12102120"],"award-info":[{"award-number":["12102120"]}]},{"name":"Theme-based Research Scheme from the Research Grants Council of the Hong Kong Special Administrative Region, China","award":["T12-201\/20-R"],"award-info":[{"award-number":["T12-201\/20-R"]}]},{"name":"Basic and Applied Basic Research Fund from Department of Science and Technology of Guangdong Province","award":["2019B1515120089"],"award-info":[{"award-number":["2019B1515120089"]}]},{"name":"Inter-institutional Collaborative Research Scheme from Hong Kong Baptist University","award":["RC-ICRS\/19-20\/01"],"award-info":[{"award-number":["RC-ICRS\/19-20\/01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aptamers are promising therapeutic and diagnostic agents for various diseases due to their high affinity and specificity against target proteins. Structural determination in combination with multiple biochemical and biophysical methods could help to explore the interacting mechanism between aptamers and their targets. Regrettably, structural studies for aptamer\u2013target interactions are still the bottleneck in this field, which are facing various difficulties. In this review, we first reviewed the methods for resolving structures of aptamer\u2013protein complexes and for analyzing the interactions between aptamers and target proteins. We summarized the general features of the interacting nucleotides and residues involved in the interactions between aptamers and proteins. Challenges and perspectives in current methodologies were discussed. Approaches for determining the binding affinity between aptamers and target proteins as well as modification strategies for stabilizing the binding affinity of aptamers to target proteins were also reviewed. The review could help to understand how aptamers interact with their targets and how alterations such as chemical modifications in the structures affect the affinity and function of aptamers, which could facilitate the optimization and translation of aptamers-based theranostics.<\/jats:p>","DOI":"10.3390\/ijms22084093","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T12:11:00Z","timestamp":1618488660000},"page":"4093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Structural Biology for the Molecular Insight between Aptamers and Target Proteins"],"prefix":"10.3390","volume":"22","author":[{"given":"Ning","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7690-8651","authenticated-orcid":false,"given":"Zihao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingdong","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China"},{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone &amp; Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China"},{"name":"Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5103-1681","authenticated-orcid":false,"given":"Hewen","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zong-Kang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Lu","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China"},{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone &amp; Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China"},{"name":"Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China"},{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone &amp; Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China"},{"name":"Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7807-7695","authenticated-orcid":false,"given":"Ge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong Macao Greater Bay Area International Research Platform for Aptamer-Based Translational Medicine and Drug Discovery, Hong Kong, China"},{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone &amp; Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China"},{"name":"Institute of Integrated Bioinformedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/346818a0","article-title":"In vitro selection of RNA molecules that bind specific ligands","volume":"346","author":"Ellington","year":"1990","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s40291-019-00400-6","article-title":"Aptamers as therapeutic agents: Has the initial euphoria subsided?","volume":"23","author":"Mayer","year":"2019","journal-title":"Mol. 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