Leveraging Cross-Linking Mass Spectrometry for Modeling Antibody-Antigen Complexes
Andrea Di Ianni1,2, Alessio Di Ianni3, Kyra Cowan4
1NBE-DMPK Innovative BioAnalytics, Merck Serono RBM S.p.A., an Affiliate of Merck KGaA, Darmstadt, Germany, Via Ribes 1, Colleretto Giacosa (TO) 10010, Italy.
Journal of Proteome Research
|February 19, 2024
Summary
Cross-linking mass spectrometry (XL-MS) aids in mapping antibody-antigen interactions. This study demonstrates XL-MS data
Area of Science:
- Structural Biology
- Immunology
- Computational Biology
Background:
- Understanding antibody-antigen complexes at the atomic level is crucial for immune response insights and therapeutic development.
- Cross-linking mass spectrometry (XL-MS) is a valuable technique for mapping protein-protein interactions and providing structural information.
- The application of XL-MS for epitope/paratope mapping in antibody-antigen complexes remains underexplored.
Purpose of the Study:
- To investigate the impact of XL-MS data on the integrative modeling of antibody-antigen complexes.
- To leverage XL-MS data for precise determination of antibody-antigen binding interfaces.
- To enhance the design of protein therapeutics and vaccines through improved structural insights.
Main Methods:
- Applied XL-MS to three distinct antibody-antigen complexes to gather binding interface information.
- Utilized XL-MS data to drive integrative modeling using HADDOCK and AlphaLink2.
- Compared the modeling results with initial predictions generated by AlphaFold Multimer.
Main Results:
- XL-MS data successfully informed integrative modeling approaches, providing distance restraints for binding interface determination.
- The study identified specific cross-links informative for modeling antibody-antigen interactions.
- Comparison revealed the contribution of XL-MS data in refining structural predictions compared to standalone methods.
Conclusions:
- XL-MS data significantly enhances the accuracy of integrative modeling for antibody-antigen complexes.
- The integration of XL-MS data is vital for resolving conformational dynamics and precise binding interface mapping.
- This approach holds promise for advancing the development of novel protein therapeutics and vaccines.
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