The design of PROteolysis TArgeting Chimeras (PROTACs) requires bringing an E3 ligase<br/>into proximity with a target protein, to modulate the concentration of the latter through its ubiquitination and degradation. Here we present a method for generating high-accuracy structural models of E3 ligase-PROTAC-target protein ternary complexes. The method is dependent on two computational innovations; adding a “silent” convolution term to an efficient protein-protein docking program to eliminate protein poses that do not have acceptable linker conformations, and clustering models of multiple PROTACs that use the same E3 ligase and target the same protein. The method is demonstrated by applications to known PROTAC structures.

Computational prediction of PROTAC complex structures

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.