Protein-protein interaction prediction in the pre- and post-AlphaFold era: the 8th CAPRI evaluation

We report on the 8th CAPRI Evaluation period, capturing the assessment of CAPRI Rounds 47 to 55 (excluding the CASP and COVID-related Rounds), which have witnessed the transition to AI-driven prediction tools such as AlphaFold and related alternatives. The prediction Rounds in this evaluation are characterized by a high level of difficulty due to various factors including the nature of the targets, the intricacy of the interfaces to be predicted and conformational changes. A total of 11 targets encompassing 21 interfaces, mostly in the difficult prediction category, were evaluated. While a retrospective analysis reveals a strong performance of AlphaFold on those targets, human predictors still outperform AI on difficult targets, particularly those involving antibodies and nucleic acids. Almost 25 years after its birth, CAPRI remains a vibrant and collaborative initiative with active participation from approximately 50 predictor and scorer groups, and 10 servers. Continued contributions from experimentalists providing targets to such blind experiments, and further advances in AI, sampling strategies and improvement in scoring methods will be key to overcoming remaining structural prediction challenges in complex biomolecular systems.