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Growing evidence suggests that the MPXV surface protein A29 could be a specific diagnostic marker for immunological detection. In this study, a fully synthetic phage display library was screened, revealing two nanobodies (A1 and H8) that specifically recognize A29. Subsequently, an in vitro affinity maturation strategy based on computer-aided design was proposed by building and docking the A29 and A1 three-dimensional structures. Ligand-receptor binding and molecular dynamics simulations were performed to predict binding modes and key residues. Three mutant antibodies were predicted using the platform, increasing the affinity by approximately 10-fold compared with the parental form. These results will facilitate the application of computers in antibody optimization and reduce the cost of antibody development; moreover, the predicted antibodies provide a reference for establishing an immunological response against MPXV.<\/jats:p>","DOI":"10.3390\/molecules28196838","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T07:50:26Z","timestamp":1695887426000},"page":"6838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9074-9784","authenticated-orcid":false,"given":"Haiyang","family":"Yu","sequence":"first","affiliation":[{"name":"School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China"},{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanchao","family":"Mao","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhipeng","family":"Pei","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinfeng","family":"Cen","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqi","family":"Meng","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songling","family":"Li","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxue","family":"Sun","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Xiao","sequence":"additional","affiliation":[{"name":"Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China"},{"name":"Marine Biomedical Science and Technology Innovation Platform of Lingang Special Area, Shanghai 201306, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022). Multi-Country Outbreak of Monkeypox. External Situation Report 2, World Health Organization."},{"key":"ref_2","unstructured":"WHO (2023). 2022\u20132023 Mpox Outbreak: Global Trends, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1093\/ije\/17.3.643","article-title":"The transmission potential of monkeypox virus in human populations","volume":"17","author":"Fine","year":"1988","journal-title":"Int. J. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13454","DOI":"10.1128\/JVI.79.21.13454-13462.2005","article-title":"Combinations of polyclonal or monoclonal antibodies to proteins of the outer membranes of the two infectious forms of vaccinia virus protect mice against a lethal respiratory challenge","volume":"79","author":"Lustig","year":"2005","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102855","DOI":"10.1016\/j.jaut.2022.102855","article-title":"The 2022 outbreak and the pathobiology of the monkeypox virus","volume":"131","author":"Kumar","year":"2022","journal-title":"J. Autoimmun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.cell.2016.09.049","article-title":"Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections","volume":"167","author":"Gilchuk","year":"2016","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e0150421","DOI":"10.1128\/JVI.01504-21","article-title":"A Nucleic Acid-Based Orthopoxvirus Vaccine Targeting the Vaccinia Virus L1, A27, B5, and A33 Proteins Protects Rabbits against Lethal Rabbitpox Virus Aerosol Challenge","volume":"96","author":"Mucker","year":"2022","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1146\/annurev-immunol-042617-053327","article-title":"Exploiting Nanobodies\u2019 Singular Traits","volume":"36","author":"Ingram","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ab.2015.09.023","article-title":"Identification and characterization of species-specific nanobodies for the detection of Listeria monocytogenes in milk","volume":"493","author":"Tu","year":"2016","journal-title":"Anal. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.ijpara.2019.03.004","article-title":"An innovative approach in the detection of Toxocara canis excretory\/secretory antigens using specific nanobodies","volume":"49","author":"Sariego","year":"2019","journal-title":"Int. J. Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.molimm.2018.02.012","article-title":"Recent advances in the selection and identification of antigen-specific nanobodies","volume":"96","author":"Liu","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1080\/07357907.2018.1458858","article-title":"Nanobodies and Cancer: Current Status and New Perspectives","volume":"36","author":"Allegra","year":"2018","journal-title":"Cancer Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"386","DOI":"10.7150\/thno.8006","article-title":"Nanobody: The \u201cmagic bullet\u201d for molecular imaging?","volume":"4","author":"Chakravarty","year":"2014","journal-title":"Theranostics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1093\/protein\/gzy017","article-title":"Analysis of nanobody paratopes reveals greater diversity than classical antibodies","volume":"31","author":"Mitchell","year":"2018","journal-title":"Protein Eng. Des. Sel. PEDS"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4369","DOI":"10.1016\/j.jmb.2018.09.002","article-title":"Structural Basis of Epitope Recognition by Heavy-Chain Camelid Antibodies","volume":"430","author":"Zavrtanik","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/j.drudis.2022.05.002","article-title":"Advances in antibody phage display technology","volume":"27","author":"Ledsgaard","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1056\/NEJMcibr1903249","article-title":"Phage Display to Detect and Identify Autoantibodies in Disease","volume":"381","author":"Deutscher","year":"2019","journal-title":"New Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.biotechadv.2010.07.004","article-title":"Phage display: Concept, innovations, applications and future","volume":"28","author":"Pande","year":"2010","journal-title":"Biotechnol. Adv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ijbiomac.2022.03.113","article-title":"An overview on display systems (phage, bacterial, and yeast display) for production of anticancer antibodies; advantages and disadvantages","volume":"208","author":"Mahdavi","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.1039\/C7CP08116B","article-title":"Binding affinity prediction of nanobody-protein complexes by scoring of molecular dynamics trajectories","volume":"20","author":"Soler","year":"2018","journal-title":"Phys. Chem. Chem. Phys. PCCP"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.pbiomolbio.2014.07.004","article-title":"An overview of recent advances in structural bioinformatics of protein-protein interactions and a guide to their principles","volume":"116","author":"Sudha","year":"2014","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/nbt752","article-title":"Generation and iterative affinity maturation of antibodies in vitro using hypermutating B-cell lines","volume":"20","author":"Cumbers","year":"2002","journal-title":"Nat. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1080\/07391102.2012.706073","article-title":"Affinity maturation of antiHER2 monoclonal antibody MIL5 using an epitope-specific synthetic phage library by computational design","volume":"31","author":"Qiao","year":"2013","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev-bioeng-071114-040733","article-title":"Advances in Antibody Design","volume":"17","author":"Tiller","year":"2015","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kiyoshi, M., Caaveiro, J.M., Miura, E., Nagatoishi, S., Nakakido, M., Soga, S., Shirai, H., Kawabata, S., and Tsumoto, K. (2014). Affinity improvement of a therapeutic antibody by structure-based computational design: Generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087099"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W469","DOI":"10.1093\/nar\/gkw458","article-title":"mCSM-AB: A web server for predicting antibody-antigen affinity changes upon mutation with graph-based signatures","volume":"44","author":"Pires","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1093\/bioinformatics\/btz779","article-title":"mCSM-AB2: Guiding rational antibody design using graph-based signatures","volume":"36","author":"Myung","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.csbj.2018.01.002","article-title":"FoldX as Protein Engineering Tool: Better Than Random Based Approaches?","volume":"16","author":"Rudat","year":"2018","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100939","DOI":"10.1016\/j.isci.2020.100939","article-title":"MutaBind2: Predicting the Impacts of Single and Multiple Mutations on Protein-Protein Interactions","volume":"23","author":"Zhang","year":"2020","journal-title":"iScience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W333","DOI":"10.1093\/nar\/gkt450","article-title":"BeAtMuSiC: Prediction of changes in protein-protein binding affinity on mutations","volume":"41","author":"Dehouck","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2021.07.054","article-title":"Positive charge in the complementarity-determining regions of synthetic nanobody prevents aggregation","volume":"572","author":"Zhong","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1021\/acs.jcim.1c00341","article-title":"NLDock: A Fast Nucleic Acid-Ligand Docking Algorithm for Modeling RNA\/DNA-Ligand Complexes","volume":"61","author":"Feng","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.drudis.2021.10.013","article-title":"Docking and scoring for nucleic acid-ligand interactions: Principles and current status","volume":"27","author":"Feng","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: Fast, flexible, and free","volume":"26","author":"Lindahl","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/jb\/mvt058","article-title":"Affinity maturation of a CDR3-grafted VHH using in silico analysis and surface plasmon resonance","volume":"154","author":"Inoue","year":"2013","journal-title":"J. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.mimet.2013.05.013","article-title":"A SOE-PCR method of introducing multiple mutations into Mycoplasma gallisepticum neuraminidase","volume":"94","author":"Tan","year":"2013","journal-title":"J. Microbiol. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bunge, E.M., Hoet, B., Chen, L., Lienert, F., Weidenthaler, H., Baer, L.R., and Steffen, R. (2022). The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Neglected Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0010141"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/cid\/ciac622","article-title":"Antivirals With Activity Against Mpox: A Clinically Oriented Review","volume":"76","author":"Siegrist","year":"2023","journal-title":"Clin. Infect. Dis. An. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e28429","DOI":"10.1002\/jmv.28429","article-title":"Mpox diagnostics: Review of current and emerging technologies","volume":"95","author":"Lim","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Shi, D., He, P., Song, Y., Cheng, S., Linhardt, R.J., Dordick, J.S., Chi, L., and Zhang, F. (2022). Kinetic and Structural Aspects of Glycosaminoglycan-Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance. Molecules, 27.","DOI":"10.3390\/molecules27185898"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.virol.2014.06.039","article-title":"A highly specific monoclonal antibody against monkeypox virus detects the heparin binding domain of A27","volume":"464\u2013465","author":"Hughes","year":"2014","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jim.2004.12.005","article-title":"Affinity maturation of a V(H)H by mutational hotspot randomization","volume":"297","author":"Yau","year":"2005","journal-title":"J. Immunol. Methods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1038\/s41598-018-20599-4","article-title":"Application of Assisted Design of Antibody and Protein Therapeutics (ADAPT) improves efficacy of a Clostridium difficile toxin A single-domain antibody","volume":"8","author":"Sulea","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10920","DOI":"10.1073\/pnas.1512704112","article-title":"Hole hopping through tyrosine\/tryptophan chains protects proteins from oxidative damage","volume":"112","author":"Gray","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10895","DOI":"10.1074\/jbc.RA118.003650","article-title":"Structure-based stabilization of insulin as a therapeutic protein assembly via enhanced aromatic-aromatic interactions","volume":"293","author":"Rege","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1126\/science.3892686","article-title":"Aromatic-aromatic interaction: A mechanism of protein structure stabilization","volume":"229","author":"Burley","year":"1985","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"184507","DOI":"10.1063\/1.2386157","article-title":"An accurate and simple quantum model for liquid water","volume":"125","author":"Paesani","year":"2006","journal-title":"J. Chem. Phys."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1021\/ct700200b","article-title":"P-LINCS:\u2009 A Parallel Linear Constraint Solver for Molecular Simulation","volume":"4","author":"Hess","year":"2008","journal-title":"J. Chem. Theory Comput."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"075503","DOI":"10.1103\/PhysRevLett.90.075503","article-title":"Predicting crystal structures: The Parrinello-Rahman method revisited","volume":"90","author":"Laio","year":"2003","journal-title":"Phys. Rev. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1002\/pro.3633","article-title":"AbRSA: A robust tool for antibody numbering","volume":"28","author":"Li","year":"2019","journal-title":"Protein Sci. A Publ. Protein Soc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1093\/bioinformatics\/btm474","article-title":"InterProSurf: A web server for predicting interacting sites on protein surfaces","volume":"23","author":"Negi","year":"2007","journal-title":"Bioinformatics"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/19\/6838\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:00:31Z","timestamp":1760130031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/19\/6838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,28]]},"references-count":54,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["molecules28196838"],"URL":"https:\/\/doi.org\/10.3390\/molecules28196838","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,28]]}}}