Unveiling the affinity–stability relationship in anti-measles virus antibodies: a computational approach for hotspots prediction
Recent years have seen an uptick in the use of computational applications in antibody engineering. These tools have enhanced our ability to predict interactions with antigens and immunogenicity, facilitate humanization, and serve other critical functions. However, several studies highlight the conce...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1302737/full |
| _version_ | 1797289207573512192 |
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| author | Rimpa Paul Rimpa Paul Keisuke Kasahara Jiei Sasaki Jorge Fernández Pérez Ryo Matsunaga Ryo Matsunaga Takao Hashiguchi Daisuke Kuroda Daisuke Kuroda Daisuke Kuroda Kouhei Tsumoto Kouhei Tsumoto Kouhei Tsumoto |
| author_facet | Rimpa Paul Rimpa Paul Keisuke Kasahara Jiei Sasaki Jorge Fernández Pérez Ryo Matsunaga Ryo Matsunaga Takao Hashiguchi Daisuke Kuroda Daisuke Kuroda Daisuke Kuroda Kouhei Tsumoto Kouhei Tsumoto Kouhei Tsumoto |
| author_sort | Rimpa Paul |
| collection | DOAJ |
| description | Recent years have seen an uptick in the use of computational applications in antibody engineering. These tools have enhanced our ability to predict interactions with antigens and immunogenicity, facilitate humanization, and serve other critical functions. However, several studies highlight the concern of potential trade-offs between antibody affinity and stability in antibody engineering. In this study, we analyzed anti-measles virus antibodies as a case study, to examine the relationship between binding affinity and stability, upon identifying the binding hotspots. We leverage in silico tools like Rosetta and FoldX, along with molecular dynamics (MD) simulations, offering a cost-effective alternative to traditional in vitro mutagenesis. We introduced a pattern in identifying key residues in pairs, shedding light on hotspots identification. Experimental physicochemical analysis validated the predicted key residues by confirming significant decrease in binding affinity for the high-affinity antibodies to measles virus hemagglutinin. Through the nature of the identified pairs, which represented the relative hydropathy of amino acid side chain, a connection was proposed between affinity and stability. The findings of the study enhance our understanding of the interactions between antibody and measles virus hemagglutinin. Moreover, the implications of the observed correlation between binding affinity and stability extend beyond the field of anti-measles virus antibodies, thereby opening doors for advancements in antibody research. |
| first_indexed | 2024-03-07T19:00:53Z |
| format | Article |
| id | doaj.art-b704f40813704f50bdab3ee2bb5767d6 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-07T19:00:53Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-b704f40813704f50bdab3ee2bb5767d62024-03-01T14:56:38ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2024-03-011010.3389/fmolb.2023.13027371302737Unveiling the affinity–stability relationship in anti-measles virus antibodies: a computational approach for hotspots predictionRimpa Paul0Rimpa Paul1Keisuke Kasahara2Jiei Sasaki3Jorge Fernández Pérez4Ryo Matsunaga5Ryo Matsunaga6Takao Hashiguchi7Daisuke Kuroda8Daisuke Kuroda9Daisuke Kuroda10Kouhei Tsumoto11Kouhei Tsumoto12Kouhei Tsumoto13Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, JapanResearch Center of Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, JapanInstitute for Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, JapanDepartment of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, JapanDepartment of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, JapanDepartment of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, JapanInstitute for Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, JapanDepartment of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, JapanResearch Center of Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, JapanDepartment of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, JapanDepartment of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, JapanThe Institute of Medical Science, The University of Tokyo, Tokyo, JapanRecent years have seen an uptick in the use of computational applications in antibody engineering. These tools have enhanced our ability to predict interactions with antigens and immunogenicity, facilitate humanization, and serve other critical functions. However, several studies highlight the concern of potential trade-offs between antibody affinity and stability in antibody engineering. In this study, we analyzed anti-measles virus antibodies as a case study, to examine the relationship between binding affinity and stability, upon identifying the binding hotspots. We leverage in silico tools like Rosetta and FoldX, along with molecular dynamics (MD) simulations, offering a cost-effective alternative to traditional in vitro mutagenesis. We introduced a pattern in identifying key residues in pairs, shedding light on hotspots identification. Experimental physicochemical analysis validated the predicted key residues by confirming significant decrease in binding affinity for the high-affinity antibodies to measles virus hemagglutinin. Through the nature of the identified pairs, which represented the relative hydropathy of amino acid side chain, a connection was proposed between affinity and stability. The findings of the study enhance our understanding of the interactions between antibody and measles virus hemagglutinin. Moreover, the implications of the observed correlation between binding affinity and stability extend beyond the field of anti-measles virus antibodies, thereby opening doors for advancements in antibody research.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1302737/fullantibody engineeringcomputer-aided designmeasles virus hemagglutininhotspotsrelative hydropathymolecular dynamics |
| spellingShingle | Rimpa Paul Rimpa Paul Keisuke Kasahara Jiei Sasaki Jorge Fernández Pérez Ryo Matsunaga Ryo Matsunaga Takao Hashiguchi Daisuke Kuroda Daisuke Kuroda Daisuke Kuroda Kouhei Tsumoto Kouhei Tsumoto Kouhei Tsumoto Unveiling the affinity–stability relationship in anti-measles virus antibodies: a computational approach for hotspots prediction Frontiers in Molecular Biosciences antibody engineering computer-aided design measles virus hemagglutinin hotspots relative hydropathy molecular dynamics |
| title | Unveiling the affinity–stability relationship in anti-measles virus antibodies: a computational approach for hotspots prediction |
| title_full | Unveiling the affinity–stability relationship in anti-measles virus antibodies: a computational approach for hotspots prediction |
| title_fullStr | Unveiling the affinity–stability relationship in anti-measles virus antibodies: a computational approach for hotspots prediction |
| title_full_unstemmed | Unveiling the affinity–stability relationship in anti-measles virus antibodies: a computational approach for hotspots prediction |
| title_short | Unveiling the affinity–stability relationship in anti-measles virus antibodies: a computational approach for hotspots prediction |
| title_sort | unveiling the affinity stability relationship in anti measles virus antibodies a computational approach for hotspots prediction |
| topic | antibody engineering computer-aided design measles virus hemagglutinin hotspots relative hydropathy molecular dynamics |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1302737/full |
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