ProRefiner: An Entropy-based Refining Strategy for Inverse Protein Folding with Global Graph Attention

This is a demo code for paper ProRefiner: An Entropy-based Refining Strategy for Inverse Protein Folding with Global Graph Attention. You can also run the demo online through Colab or Code Ocean for easier environment setup.

File structure

We provide the ProRefiner implementation in folder model. We put the code provided by ProteinMPNN in folder ProteinMPNN. run.py contains the sequence design pipeline.

Environemnt setup

The program is written in Python. Please first install Python on the machine. Then run the following script in the terminal to setup the environment. It will automatically install the latest version of the packages.

pip install torch torchvision torchaudio
pip install biopython
pip install fairseq

We recommend running on Linux systems. The code has been tested on the latest version of the above dependencies. The setup should be completed within few minutes.

Run protein sequence design

This demo demonstrates sequence design with base model ProteinMPNN. Full sequence design and partial sequence design are supported. Designing one protein is fast with few seconds on CPUs.

Full sequence design

Run the following script to start design.

python run.py PDB_CODE_or_PDB_PATH CHAIN

For example:

python run.py 8flh A                # provide a PDB code
python run.py input/8flh.pdb A      # provide a PDB file path 

If a PDB code is provided, the PDB file will be automatically downloaded. The program will run sequence design on the specified chain (only single chain design is supported). Here is an example output of script python run.py 8flh A:

Read 8flh chain A with length 266
Recovery and nssr are computed based on designable residues with coordinates (265 residues).

native sequence:
YGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEE

sequence by ProteinMPNN: (recovery: 44.906      nssr: 59.623)
LEPWEIDPADLTYLEHLGTGPGGTVWAGLLKGKTPVAVKELKPGAFDEDALIEWLKEKMNIKHPNIVQLLGVSTGQTPILIVKEYCPKGVLLDYLRDKSRNLSPEQLLQLCLNIAKGLAYLESKNILHRDLKTGNCLVDENGVAKIADFGFIRFVRDPSARTVGSDFPYRWSPLEVLTNGNYSFASDVWSFGVTMWEIFSLGATPFAGMTNEEIIAYIKAGKTLTRPALASPAAWALAAACLAPNPADRPTFAELLAALEAILAAA

sequence by ProRefiner + ProteinMPNN: (recovery: 56.226 nssr: 72.453)
MGAWEINPADLTFLEHLGEGALGVVRKGLLKGKTKVAVKELKEGAFDIESLIADAKVKMNLKHENLVRLYGICTSQSPILLITEYMANGNLLDYLRDKSRNFSTEQLLQMCLDVCKAMAYLESKNELHRDLKSENCLVDENGVVKVSDYGLIRFVKDESARTVGSKFPVRWSPPEVLENNDYSFKSDVWSFGVTMWEIFSLGETPYESMSDEETAAWIKQGKTLTRPARASDEVWAILSSCLQADAEQRPTFAELLAQLEEVQKAE

Partial sequence design

Run the following script for partial design, where the indexes of residues to design (index starting from 1 not 0) are separated by comma.

python run.py PDB_CODE_or_PDB_PATH CHAIN INDEX1,INDEX2,INDEX3

Please note that there is no space betweem indexes. For example, to design the first 10 residues of chain A, run:

python run.py 8flh A 1,2,3,4,5,6,7,8,9,10

An example output for the above command will be:

Read 8flh chain A with length 266
Recovery and nssr are computed based on designable residues with coordinates (10 residues).

native sequence:
YGSWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEE

sequence by ProteinMPNN: (recovery: 40.000      nssr: 50.000)
LEPYEIDISDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEE

sequence by ProRefiner: (recovery: 50.000       nssr: 90.000)
MGAWEVNPEDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEE