In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design
Mpox virus (MPXV), the most pathogenic zoonotic orthopoxvirus, caused worldwide concern during the SARS-CoV-2 epidemic. 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 librar...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/19/6838 |
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| author | Haiyang Yu Guanchao Mao Zhipeng Pei Jinfeng Cen Wenqi Meng Yunqin Wang Shanshan Zhang Songling Li Qingqiang Xu Mingxue Sun Kai Xiao |
| author_facet | Haiyang Yu Guanchao Mao Zhipeng Pei Jinfeng Cen Wenqi Meng Yunqin Wang Shanshan Zhang Songling Li Qingqiang Xu Mingxue Sun Kai Xiao |
| author_sort | Haiyang Yu |
| collection | DOAJ |
| description | Mpox virus (MPXV), the most pathogenic zoonotic orthopoxvirus, caused worldwide concern during the SARS-CoV-2 epidemic. 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. |
| first_indexed | 2024-03-10T21:39:53Z |
| format | Article |
| id | doaj.art-80abc44c7cb14baf838b923660d7d77d |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T21:39:53Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-80abc44c7cb14baf838b923660d7d77d2023-11-19T14:46:19ZengMDPI AGMolecules1420-30492023-09-012819683810.3390/molecules28196838In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided DesignHaiyang Yu0Guanchao Mao1Zhipeng Pei2Jinfeng Cen3Wenqi Meng4Yunqin Wang5Shanshan Zhang6Songling Li7Qingqiang Xu8Mingxue Sun9Kai Xiao10School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaLab of Toxicology and Pharmacology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, ChinaMpox virus (MPXV), the most pathogenic zoonotic orthopoxvirus, caused worldwide concern during the SARS-CoV-2 epidemic. 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.https://www.mdpi.com/1420-3049/28/19/6838MPXVA29 proteinnanobodyin vitro affinity maturation |
| spellingShingle | Haiyang Yu Guanchao Mao Zhipeng Pei Jinfeng Cen Wenqi Meng Yunqin Wang Shanshan Zhang Songling Li Qingqiang Xu Mingxue Sun Kai Xiao In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design Molecules MPXV A29 protein nanobody in vitro affinity maturation |
| title | In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design |
| title_full | In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design |
| title_fullStr | In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design |
| title_full_unstemmed | In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design |
| title_short | In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design |
| title_sort | in vitro affinity maturation of nanobodies against mpox virus a29 protein based on computer aided design |
| topic | MPXV A29 protein nanobody in vitro affinity maturation |
| url | https://www.mdpi.com/1420-3049/28/19/6838 |
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