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

Notes:

1. All fluorine atoms should be removed, and superimposed back after ternary modeling.

2. All non-standard residues should be removed.

3. All charges should be removed, and consistent with protac smiles.

4. Only one chain is permitted for target and receptor complex.

5. All alternative positions should be removed.

6. If there is some heterocyclic structures in the pdb, they should be replaced with a similar alkyl ring and superimposed back after ternary modeling.