Installation requirements for PROTAC-MODEL: 1. Python 2.7 2. Install RDKit, ADFRsuite(https://ccsb.scripps.edu/adfr/downloads/), Vina (http://vina.scripps.edu/download.html), Voromqa(https://github.com/kliment-olechnovic/voronota), FCC (https://github.com/haddocking/fcc). 3. FRODOCK(https://chaconlab.org/modeling/frodock/frodock-donwload). This url is for the v3.12. If you want to download the v2.1, I think you can send an e-mail to the author. 4. Rosetta (https://www.rosettacommons.org/software/license-and-download). For improving the calculation efficiency, we highly recommend you to install MPI. Our scripts are also compiled based on MPI. 5. Set the following environment parameters: export ADFRSUITE=/Path/to/ADFRSUITE/ export FRODOCK=/Path/to/FRODOCK/ export VINA=/Path/to/VINA/ export VOROMQA=/Path/to/VOROMQA/ export FCC=/Path/to/FCC/ export ROSETTA=/Path/to/ROSETTA/ usage: main.py [-h] -irec <string> -ilig <string> -site X,Y,Z -ismi <string> -o <string> [-cpu <int>] [-ie3lig1 <string>] [-ie3lig2 <string>] [-refine] optional arguments: -h, --help show this help message and exit -irec <string>, --input-receptor-pdb <string> PDB file of receptor protein should include the small molecular binder and exclude other heteroatoms. Please submit the larger protein as the receptor. -ilig <string>, --input-target-pdb <string> PDB file of target protein should include the small molecular binder and exclude other heteroatoms. Please submit the smaller protein as the target. -site X,Y,Z, --input-docking-site X,Y,Z The docking site in the receptor for protein-protein docking. e.g. -site=-35.73,13.75,-27.92 -ismi <string>, --input-protac-smi <string> Smiles file of PROTAC. -o <string>, --output-filepath <string> The filepath for storing files. -cpu <int> Number of cpu to calculate. Default value: 1 -ie3lig1 <string>, --input-e3-ligand-sdf1 <string> First sdf file of the e3 ligand which contains two possible locations for the attachment of the atoms, e.g. thalidomide. -ie3lig2 <string>, --input-e3-ligand-sdf2 <string> Second sdf file of the e3 ligand which contains two possible locations for the attachment of the atoms, e.g. thalidomide. -refine, --rosettadock-refinement Use the RosettaDock-based refinement to improve the prediction performance. But it will cost much more time. Tutorials: Example 1: For FRODOCK only: python main.py -irec example_1/receptor.pdb -ilig example_1/target.pdb -site=-35.73,13.75,-27.92 -ismi example_1/protac.smi -o docking_1 -cpu 28 With RosettaDock-based refinement: python main.py -irec example_1/receptor.pdb -ilig example_1/target.pdb -site=-35.73,13.75,-27.92 -ismi example_1/protac.smi -o docking_1 -cpu 28 -refine Example 2: For FRODOCK only: python main.py -irec example_2/receptor.pdb -ilig example_2/target.pdb -site=68.02,46.63,48.63 -ismi example_2/protac.smi -o docking_2 -cpu 28 -ie3lig1 example_2/rec_lig_1.sdf -ie3lig2 example_2/rec_lig_2.sdf With RosettaDock-based refinement: python main.py -irec example_2/receptor.pdb -ilig example_2/target.pdb -site=68.02,46.63,48.63 -ismi example_2/protac.smi -o docking_2 -cpu 28 -ie3lig1 example_2/rec_lig_1.sdf -ie3lig2 example_2/rec_lig_2.sdf -refine If you meet some problems, please contact wenggaoqi@zju.edu.cn