Generating PROTAC conformations in the
context of the protein–protein
interaction. Using RDKit, we generate up to 100 PROTAC conformations,
to match the ligand orientation of each local docking solution. Then,
we use Rosetta Packer to choose the best conformation to fit the protein–protein
docking model. A. An example local docking solution for 6BOY. B. The ligand orientation,
extracted from the local docking solution. C. Constrained conformations
that bridge between the ligand orientation. D. Output model of Rosetta
after choosing the best constrained conformation. E. The conformation
chosen by Rosetta. Green, E3 ligase CRBN; cyan, predicted BRD4; light
pink, predicted PROTAC conformation.