A comprehensive primer and review of PROTACs and their In Silico design

Jacopo Zattoni, Paola Vottero, Gea Carena, Chiara Uliveto, Giulia Pozzati, Benedetta Morabito, Ebenezea Gitari, Jack A. Tuszynski, Maral Aminpour

Abstract: Highlights•Prior protein-protein docking greatly increases the success of structure-based design•The Rosetta suite excels among structure-based ternary complex prediction methods•Lysine density in ubiquitination zone reliably predicts degradation efficiency•Deep learning can model ligand-dependent multicomponent assemblies’ conformations•AlphaFold and RosettaFold trained on experimental data can reshape PROTAC design