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Protein design framework

This repository present the protein design framework described in the paper. The fixed-backbone protein sequence design model (PSdesign) were built based on AlphaDesign. We also fine-tuned the ESM2 model to get a specialized version, ESM2_TadA. These codes are only available for non-commercial usage.

Requirements

The following python packages are required.

  • numpy, pandas
  • pytorch
  • torch_scatter
  • ESM2
  • biotite

Step1. Train the protein design model

$ python train_test_design_fp16_v13v3best2.py

Step2. Fine-tune the protein design model for TadA

Before runing this script, you need to prepare the dataset( using ESMFold to generated pdb files). Then set the path of checkpoint for the pre-tained model from step1. The esmfold_inference.py file is directly from ESM2.

$ python esmfold_inference.py -i seqdump_8e2p_top4791.fa -o esmfold/8e2p_top4791 > seqdump_8e2p_top4791.log
$ python train_test_design_fp16_v13v3best2_tadA.py

Step3. Fine-tune the ESM2 model for TadA

Prepare the dataset: Execute PREdata_TadA.py, providing the fasta file as input, and obtain pt files stored within the train_4791 and test_4791 directories.

$ python PREdata_TadA.py

In TadA_train.py, specify the paths for the train_4791 and test_4791 directories. Run the code for training. The training process will retain the optimal model based on the loss on the test set. Multi-GPU training is supported in the training process. Example usage:

$ CUDA_VISIBLE_DEVICES=0,1 python TadA_train.py

Step4. Generate probability distribution

Before runing this script, you need to set the path of checkpoint for the fine-tuned model from step2.

$ python run_predict_proteindesign_v3_tadA.py -i 8e2p.chainA.pdb -o finetune_tada_8e2p

Step5. Protein sequence generation

$ python generate_tada_sequences.py

Citation

Please cite the following article:

Contact

Author: Dr. Guipeng Li

Email: guipeng.lee(AT)gmail.com

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