Integrative Modeling in the Age of Machine Learning: A Summary of HADDOCK Strategies in CAPRI 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.

Accelerating protein-protein interaction screens with reduced AlphaFold-Multimer sampling.

Motivation: Discovering new protein-protein interactions (PPIs) across entire proteomes offers vast potential for understanding novel protein functions and elucidate system properties within or between an organism. While recent advances in computational structural biology, particularly AlphaFold-Multimer, have facilitated this task, scaling for large-scale screenings remains a challenge, requiring significant computational resources.

Results: We evaluated the impact of reducing the number of models generated by AlphaFold-Multimer from five to one on the method's ability to distinguish true PPIs from false ones.

Modeling Protein-Glycan Interactions with HADDOCK.

The term glycan refers to a broad category of molecules composed of monosaccharide units linked to each other in a variety of ways, whose structural diversity is related to different functions in living organisms. Among others, glycans are recognized by proteins with the aim of carrying information and for signaling purposes. Determining the three-dimensional structures of protein-glycan complexes is essential both for the understanding of the mechanisms glycans are involved in and for applications such as drug design.

Towards the accurate modelling of antibody-antigen complexes from sequence using machine learning and information-driven docking.

Motivation: Antibody-antigen complex modelling is an important step in computational workflows for therapeutic antibody design. While experimentally determined structures of both antibody and the cognate antigen are often not available, recent advances in machine learning-driven protein modelling have enabled accurate prediction of both antibody and antigen structures. Here, we analyse the ability of protein-protein docking tools to use machine learning generated input structures for information-driven docking.

CAPRI-Q: The CAPRI resource evaluating the quality of predicted structures of protein complexes.

Protein interactions are essential for cellular processes. In recent years there has been significant progress in computational prediction of 3D structures of individual protein chains, with the best-performing algorithms reaching sub-Ångström accuracy. These techniques are now finding their way into the prediction of protein interactions, adding to the existing modeling approaches.