How AlphaFold 3 helps with multiscale drug discovery

Abstract

AlphaFold 3 (AF3) predicts protein ligand complexes, but the utility of its confidence scores for drug discovery remains unclear. We benchmarked AF3 interaction scores against BANDOCK+, an experimentally informed approach, using approved drugs and human protein libraries. AF3 ipTM achieved slightly higher observed aggregate disease ranking scores in a matched 1,103 protein comparison, with performance varying among individual indications. BANDOCK+ enabled substantially broader protein coverage using a computationally less demanding approach, including a 20,158 protein reference library. These findings highlight the potential of AF3 confidence scores for computational drug discovery and the tradeoffs between predictive performance and scalability.