Towards a Greener AlphaFold2 Protocol for Antibody-Antigen Modeling: Insights From CAPRI Round 55.

In the 55th round of CAPRI, we used enhanced AlphaFold2 (AF2) sampling and data-driven docking. Our AF2 protocol relies on Wallner's massive sampling approach, which combines different AF2 versions and sampling parameters to produce thousands of models per target. For T231 (an antibody-peptide complex) and T232 (PP2A:TIPRL complex), we employed a 50-fold reduced MinnieFold sampling and a custom ranking approach, leading to a top-ranking medium prediction in both cases. For T233 and T234 (two antibody bound MHC I complexes), we followed data-driven docking, which did not lead to an acceptable model. Our post-CAPRI55 analysis showed that if we had used our MinnieFold approach on T233 and T234, we could have submitted a medium-quality model for T233 as well. In the scoring challenge, we utilized the scoring function of FoldX, which was effective in selecting acceptable models for T231 and medium-quality models for T232. Our success, especially in predicting and ranking a medium-quality model for T231 and potentially for T233, underscores the feasibility of green and accurate enhanced AF2 sampling in antibody complex prediction.