Integrative Modeling in the Age of Machine Learning: A Summary of <scp>HADDOCK</scp> Strategies in <scp>CAPRI</scp> Rounds 47–55
The HADDOCK team participated in CAPRI rounds 47-55 as server, manual predictor, and scorers. Throughout these CAPRI rounds, we used a plethora of computational strategies to predict the structure of protein complexes. Of the 10 targets comprising 24 interfaces, we achieved acceptable or better models for 3 targets in the human category and 1 in the server category. Our performance in the scoring challenge was slightly better, with our simple scoring protocol being the only one capable of identifying an acceptable model for Target 234. This result highlights the robustness of the simple, fully physics-based HADDOCK scoring function, especially when applied to highly flexible antibody-antigen complexes. Inspired by the significant advances in machine learning for structural biology and the dramatic improvement in our success rates after the public release of Alphafold2, we identify the integration of classical approaches like HADDOCK with AI-driven structure prediction methods as a key strategy for improving the accuracy of model generation and scoring.
Authors
- Manon Réau (ORCID: https://orcid.org/0000-0002-3862-8990)
- Anna Engel (ORCID: https://orcid.org/0000-0003-1153-2101)
- Brian Jiménez‐García (ORCID: https://orcid.org/0000-0001-7786-2109)
- Zuzana Jandová (ORCID: https://orcid.org/0000-0002-4890-344X)
- Panagiotis I. Koukos (ORCID: https://orcid.org/0000-0001-6705-2815)
- Marco Giulini (ORCID: https://orcid.org/0000-0002-2691-712X)
- João M. C. Teixeira (ORCID: https://orcid.org/0000-0002-9113-0622)
- Alexandre M. J. J. Bonvin (ORCID: https://orcid.org/0000-0001-7369-1322)
- Cunliang Geng (ORCID: https://orcid.org/0000-0002-1409-8358)
- Vlad Cojocaru (ORCID: https://orcid.org/0000-0003-0886-3401)
- Victor Reys (ORCID: https://orcid.org/0000-0001-5301-317X)
- Rodrigo V. Honorato (ORCID: https://orcid.org/0000-0001-5267-3002)
- Francesco Ambrosetti
- Siri C. van Keulen (ORCID: https://orcid.org/0000-0001-6995-8389)
- Jorge Roel‐Touris (ORCID: https://orcid.org/0000-0002-6588-624X)
- Charlotte van Noort
- Xiaotong Xu (ORCID: https://orcid.org/0009-0006-1883-6692)
Institutions
- Novartis (Switzerland) (CH)
- Utrecht University (NL)
- Academy of Athens (GR)
- Babeș-Bolyai University (RO)
- Boehringer Ingelheim (Austria) (AT)
- Institut de Biologia Molecular de Barcelona (ES)
Publication Details
- Journal
- Proteins Structure Function and Bioinformatics
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1002/prot.26789
- Citations
- 3
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 1.21
Funders
- Netherlands eScience Center
- European Commission
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Horizon 2020 Framework Programme