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ProteinDT: A Text-guided Protein Design Framework
Authors: Shengchao Liu, Yanjing Li, Zhuoxinran Li, Anthony Gitter, Yutao Zhu, Jiarui Lu, Zhao Xu, Weili Nie, Arvind Ramanathan, Chaowei Xiao<sup>*</sup>, Jian Tang<sup>*</sup>, Hongyu Guo<sup>*</sup>, Anima Anandkumar<sup>*</sup>
<sup>*</sup> jointly supervised
[Project Page] [ArXiv] [Datasets on HuggingFace] [Checkpoints on HuggingFace]
<p align="center"> <img src="figures/pipeline.png" /> </p> <p align="left"> <img src="figures/final.gif" width="100%" /> </p>1 Environment
conda create -n ProteinDT python=3.7
conda activate ProteinDT
conda install -y numpy networkx scikit-learn
pip install torch==1.10.*
pip install transformers
pip install lxml
# for TAPE
pip install lmdb
pip install seqeval
# for baseline ChatGPT
pip install openai
# for baseline Galactica
pip install accelerate
# for visualization
pip install matplotlib
# for binding editing
pip install h5py
pip install torch_geometric==2.0 torch_scatter torch_sparse torch_cluster
pip install biopython
# for ESM folding
pip install "fair-esm[esmfold]"
pip install dm-tree omegaconf ml-collections einops
pip install fair-esm[esmfold]==2.0.0 --no-dependencies # Override deepspeed==0.5
pip install 'dllogger @ git+https://github.com/NVIDIA/dllogger.git'
pip install 'openfold @ git+https://github.com/aqlaboratory/openfold.git@4b41059694619831a7db195b7e0988fc4ff3a307'
conda install -c conda-forge -yq mdtraj
# for ProteinDT
pip install .
2 Pretraining Datasets (SwissProtCLAP) Preparation
Please check folder preprocess/SwissProtCLAP
for SwissProtCLAP construction from UniProt.
We also provide a copy of SwissProtCLAP at this HuggingFace link. Or you can use the following script:
from huggingface_hub import HfApi, snapshot_download
api = HfApi()
snapshot_download(repo_id="chao1224/ProteinDT", repo_type="dataset", cache_dir='./')
Then move the data under ./data
folder. The data structure is
./data/
└── SwissProtCLAP
├── protein_sequence.txt
└── text_sequence.txt
3 Pretraining
Go to folder examples
, and do the pretraining in 5 steps. We summarize the logics of these 5 steps as below:
The pretrained checkpoints can be found at this HuggingFace link.
Before getting started, first we need to define our output home folder, e.g., export OUTPUT_DIR=../output/ProteinDT/hyper_01
.
-
Step 1. Conduct CLAP pretraining
-
On a single GPU card:
python pretrain_step_01_CLAP.py \ --protein_lr=1e-5 --protein_lr_scale=1 \ --text_lr=1e-5 --text_lr_scale=1 \ --protein_backbone_model=ProtBERT_BFD \ --epochs=10 --batch_size=9 --num_workers=0 \ --output_model_dir="$OUTPUT_DIR"
-
We also support distribution learning with DDP. Example of using a server with 8 GPU cards:
CUDA_VISIBLE_DEVICES=0,1,2,3,4,5,6,7 \ python pretrain_step_01_CLAP.py \ --protein_lr=1e-5 --protein_lr_scale=1 \ --text_lr=1e-5 --text_lr_scale=1 \ --protein_backbone_model=ProtBERT_BFD \ --epochs=10 --batch_size=9 --num_workers=0 \ --output_model_dir="$OUTPUT_DIR"
-
-
Step 2. Obtain frozen representation:
python pretrain_step_02_empty_sequence.py \ --protein_backbone_model=ProtBERT_BFD \ --batch_size=16 --num_workers=0 \ --pretrained_folder="$OUTPUT_DIR" python pretrain_step_02_pairwise_representation.py \ --protein_backbone_model=ProtBERT_BFD \ --batch_size=16 --num_workers=0 \ --pretrained_folder="$OUTPUT_DIR"
-
Step 3. Learn the facilitator distribution:
python pretrain_step_03_facilitator.py \ --protein_lr=1e-5 --protein_lr_scale=1 \ --text_lr=1e-5 --text_lr_scale=1 \ --protein_backbone_model=ProtBERT_BFD \ --epochs=10 --batch_size=9 --num_workers=0 \ --pretrained_folder="$OUTPUT_DIR" \ --output_model_folder="$OUTPUT_DIR"/step_03_Gaussian_10
-
Step 4. Learn the decoder distribution. Notice that we have three types of decoder distribution models:
- A Transformer-based auto-regressive decoder. Here we adopt the T5 architecture.
python pretrain_step_04_decoder.py \ --num_workers=0 --lr=1e-4 --epochs=50 \ --decoder_distribution=T5Decoder \ --score_network_type=T5Base \ --hidden_dim=16 \ --pretrained_folder="$OUTPUT_DIR" \ --output_folder="$OUTPUT_DIR"/step_04_T5
- A discrete denoising diffusion model (multinomial diffusion).
-
Using RNN as score network:
python pretrain_step_04_decoder.py \ --num_workers=0 --lr=1e-4 --epochs=50 \ --decoder_distribution=MultinomialDiffusion \ --score_network_type=RNN \ --hidden_dim=16 \ --pretrained_folder="$OUTPUT_DIR" \ --output_folder="$OUTPUT_DIR"/step_04_MultiDiffusion_RNN
-
Using BERT as score network:
python pretrain_step_04_decoder.py \ --num_workers=0 --lr=1e-4 --epochs=50 \ --decoder_distribution=MultinomialDiffusion \ --score_network_type=BertBase \ --hidden_dim=16 \ --pretrained_folder="$OUTPUT_DIR" \ --output_folder="$OUTPUT_DIR"/step_04_MultiDiffusion_BERT
-
- A Transformer-based auto-regressive decoder. Here we adopt the T5 architecture.
-
Step 5. learn an auto-encoder that is specifically designed for text-guided editing task. You can also treat this as a downstream task.
python pretrain_step_05_AE.py \ --num_workers=0 --lr=1e-4 --epochs=50 \ --pretrained_folder="$OUTPUT_DIR" \ --output_folder="$OUTPUT_DIR"/step_05
4 Downstream Tasks
We include three types of downstream tasks, as will be introduced below. You can find the scripts for first two downstream tasks under folder scripts
.
4.1 Text-to-Protein Generation
First let's go to the folder examples/downstream_Text2Protein
.
Then we sample text sequences for text-to-protein generation:
python step_01_text_retrieval.py
We also provide the sampled text data in step_01_text_retrieval.txt
. You can replace it with the text sequences you want to use.
Now we can do the text-to-sequence generation, e.g., if we use T5 as the decoder:
export OUTPUT_DIR=../../output/ProteinDT/hyper_01
python step_02_inference_ProteinDT.py \
--decoder_distribution=T5Decoder --score_network_type=T5Base \
--num_workers=0 --hidden_dim=16 --batch_size=8 \
--pretrained_folder="$OUTPUT_DIR" \
--step_04_folder="$OUTPUT_DIR"/step_04_T5 \
--num_repeat=16 --use_facilitator --AR_generation_mode=01 \
--output_text_file_path="$OUTPUT_DIR"/step_04_T5/downstream_Text2Protein/step_02_inference.txt
4.2 Zero-shot Text-guided Protein Editing
First let's go to the folder examples/downstream_Editing
.
The dataset preparation can be found at examples/downstream_Edting/README.md
. You can also find it on this HuggingFace link. We include three types of editing tasks: stability, structure, and peptide binding. In terms of the methods, we have two types: latent optimization and latent interpolation. The demo scripts are explained below.
4.2.1 Latent Optimization
- Structure / Stability:
editing_task: alpha, beta, Villin, Pin1
.export OUTPUT_DIR=../../output/ProteinDT/hyper_01 python step_01_editing_latent_optimization.py \ --num_workers=0 --batch_size=8 \ --lambda_value=0.9 --num_repeat=16 --oracle_mode=text --temperature=2 \ --editing_task=alpha --text_prompt_id=101 \ --pretrained_folder="$OUTPUT_DIR" \ --step_05_folder="$OUTPUT_DIR"/step_05_AE \ --output_folder="$OUTPUT_DIR"/step_05_AE/downstream_Editing_latent_optimization/alpha_prompt_101_lambda_0.9_num_repeat_16_oracle_text_T_2 \ --output_text_file_path="$OUTPUT_DIR"/step_05_AE/downstream_Editing_latent_optimization/alpha_prompt_101_lambda_0.9_num_repeat_16_oracle_text_T_2/step_01_editing.txt python step_01_evaluate_structure.py \ --num_workers=0 --batch_size=8 --editing_task=alpha --text_prompt_id=101 \ --output_folder="$OUTPUT_DIR"/step_05_AE/downstream_Editing_latent_optimization/alpha_prompt_101_lambda_0.9_num_repeat_16_oracle_text_T_2 \ --output_text_file_path="$OUTPUT_DIR"/step_05_AE/downstream_Editing_latent_optimization/alpha_prompt_101_lambda_0.9_num_repeat_16_oracle_text_T_2/step_01_editing.txt
- Peptide binding
export OUTPUT_DIR=../../output/ProteinDT/hyper_01 python step_01_editing_latent_optimization.py \ --num_workers=0 --batch_size=4 \ --lambda_value=0.9 --num_repeat=16 --oracle_mode=text --temperature=2 \ --editing_task=peptide_binding --text_prompt_id=101 \ --pretrained_folder="$OUTPUT_DIR" \ --step_05_folder="$OUTPUT_DIR"/step_05_AE \ --output_folder="$OUTPUT_DIR"/step_05_AE/downstream_Editing_latent_optimization/peptide_binding_prompt_101_lambda_0.9_num_repeat_16_oracle_text_T_2 \ --output_text_file_path="$OUTPUT_DIR"/step_05_AE/downstream_Editing_latent_optimization/peptide_binding_prompt_101_lambda_0.9_num_repeat_16_oracle_text_T_2/step_02_editing.txt
4.2.2 Latent Interpolation
Notice that for latent interpolation, we have three models: auto-regressive (T5), denoising diffusion model (RNN and BERT). We provide demos scripts using T5.
- Structure / Stability:
editing_task: alpha, beta, Villin, Pin1
.export OUTPUT_DIR=../../output/ProteinDT/hyper_01 python step_01_editing_latent_interpolation.py \ --editing_task=alpha --text_prompt_id=101 \ --decoder_distribution=T5Decoder --score_network_type=T5Base \ --num_workers=0 --hidden_dim=16 --batch_size=2 \ --theta=0.9 --num_repeat=16 --oracle_mode=text --AR_generation_mode=01 --AR_condition_mode=expanded \ --pretrained_folder="$OUTPUT_DIR" --step_04_folder="$OUTPUT_DIR"/step_04_T5 \ --output_folder="$OUTPUT_DIR"/step_04_T5/downstream_Editing_latent_interpolation_alpha/prompt_101_theta_0.9_num_repeat_16_oracle_text_inference_01_expanded \ --output_text_file_path="$OUTPUT_DIR"/step_04_T5/downstream_Editing_latent_interpolation_alpha/prompt_101_theta_0.9_num_repeat_16_oracle_text_inference_01_expanded/step_01_editing.txt python step_01_evaluate_structure.py \ --num_workers=0 --batch_size=1 \ --editing_task=alpha --text_prompt_id=101 \ --output_folder="$OUTPUT_DIR"/step_04_T5/downstream_Editing_latent_interpolation_alpha/prompt_101_theta_0.9_num_repeat_16_oracle_text_inference_01_expanded \ --output_text_file_path="$OUTPUT_DIR"/step_04_T5/downstream_Editing_latent_interpolation_alpha/prompt_101_theta_0.9_num_repeat_16_oracle_text_inference_01_expanded/step_01_editing.txt
- Peptide binding
export OUTPUT_DIR=../../output/ProteinDT/hyper_01 python step_02_binding_editing_latent_interpolation.py \ --editing_task=peptide_binding --text_prompt_id=101 \ --decoder_distribution=T5Decoder --score_network_type=T5Base \ --num_workers=0 --hidden_dim=16 --batch_size=1 \ --theta=0.9 --num_repeat=16 --oracle_mode=text --AR_generation_mode=01 --AR_condition_mode=expanded \ --pretrained_folder="$OUTPUT_DIR" --step_04_folder="$OUTPUT_DIR"/step_04_T5 \ --output_folder="$OUTPUT_DIR"/step_04_T5/downstream_Editing_latent_interpolation_peptide_binding/prompt_101_theta_0.9_num_repeat_16_oracle_text_inference_01_expanded \ --output_text_file_path="$OUTPUT_DIR"/step_04_T5/downstream_Editing_latent_interpolation_peptide_binding/prompt_101_theta_0.9_num_repeat_16_oracle_text_inference_01_expanded/step_02_editing.txt
4.3 Protein Property Prediction
First please download the TAPE data following instructions here. We also provide it at this HuggingFace link.
Under examples
, and the script is downstream_TAPE.py
. We follow the exactly same hyper-parameter as OntoProtein.
python downstream_TAPE.py \
--task_name=ss3 \
--seed=3 \
--learning_rate=3e-5 \
--num_train_epochs=5 \
--per_device_train_batch_size=2 \
--gradient_accumulation_steps=8 \
--warmup_ratio=0.08 \
--pretrained_model=ProteinDT \
--pretrained_folder="$OUTPUT_DIR" \
--output_dir="$OUTPUT_DIR"/downstream_TAPE
Cite Us
Feel free to cite this work if you find it useful to you!
@article{liu2023text,
title={A Text-guided Protein Design Framework},
author={Shengchao Liu, Yanjing Li, Zhuoxinran Li, Anthony Gitter, Yutao Zhu, Jiarui Lu, Zhao Xu, Weili Nie, Arvind Ramanathan, Chaowei Xiao, Jian Tang, Hongyu Guo, Anima Anandkumar},
journal={arXiv preprint arXiv:2302.04611},
year={2023}
}