For any help regarding the server, feel free to contact us using the email addresses below. For more information about the algorithm, you are welcome to read the paper:
Zaidman D, Prilusky J, London N. PRosettaC: Rosetta based modeling of PROTAC mediated ternary complexes. J Chem Inf Model. 2020 Sep 25. PubMed:32976709 doi:http://dx.doi.org/10.1021/acs.jcim.0c00589.
Possible issues and notes:
In our work, we always used the E3 ligase as the first protein and the degradation target as the second. Generally, due to the asymmetrical property of the global docking step, it is better to submit the bigger protein as the first and the smaller as the second.
The .sdf (or PDB) files you provide for either the E3 ligase binder or protein binder, do not necessarily need to be exactly the same as the provided SMILES (i.e. a single methyl change or some additional groups are tolerated, we are aware that structures are not always available for your exact ligand). However, they should have a substantial common substructure with the provided ligands, for the protocol to execute properly.
If you choose to load the ligand as an .sdf file, note that it should represent the bound 3D conformation of the ligand in its appropriate structure (and not just a 2D chemical structure of the ligand).