Mega PROTAC, Mega Dock-Based PROTAC Mediated Ternary Complex Formation Pipeline With Sequential Filtering and Rank Aggregation

MEGA PROTAC is a novel pipeline designed to improve the prediction and ranking of ternary structures in PROTAC-mediated complex formation. It utilizes MEGADOCK for initial docking of protein-protein complexes, followed by a sequential filtration strategy and rank aggregation to refine candidate complexes. MEGA PROTAC was tested on 22 cases and outperformed the existing Bayesian optimization method (BOTCP) in 16 cases, achieving an 18% higher mean and 35% higher median DockQ score. It also demonstrated superior ranking and reduced cluster numbers, with a twofold improvement in locating acceptable DockQ scores and a higher proportion of near-native structures.