HZWzzl/genmol_image_ubuntu22.04

GenMol: A Drug Discovery Generalist with Discrete Diffusion

This is the official code repository for the paper titled GenMol: A Drug Discovery Generalist with Discrete Diffusion (ICML 2025).

Contribution

• We introduce GenMol, a model for unified and versatile molecule generation by building masked discrete diffusion that generates SAFE molecular sequences.
• We propose fragment remasking, an effective strategy for exploring chemical space using molecular fragments as the unit of exploration.
• We propose molecular context guidance (MCG), a guidance scheme for GenMol to effectively utilize molecular context information.
• We validate the efficacy and versatility of GenMol on a wide range of drug discovery tasks.

Installation

Option 1: Docker 容器（推荐，最简单）

如果你有 NVIDIA GPU，推荐使用预构建的 Docker 容器：

# 下载（约 10GB，需要等待）
git clone https://huggingface.co/datasets/HZWzzl/genmol_image_ubuntu22.04
cd genmol_image_ubuntu22.04

# 合并文件
cat genmol-container.tar.part-* > genmol-container.tar

# 加载到 Docker
docker load < genmol-container.tar

# 运行
docker run --rm -it --gpus all genmol:latest

详细步骤见 HOW_TO_USE.md

Option 2: 手动安装环境

Clone this repository:

git clone https://github.com/NVIDIA-Digital-Bio/genmol.git
cd genmol

Run the following command to install the dependencies:

bash env/setup.sh

Run the following command if you encounter the ImportError: libXrender.so.1 error:

apt update && apt install -y libsm6 libxext6 && apt-get install -y libxrender-dev

Run the following command if you encounter the ImportError: cannot import name '_CONFIG_FOR_DOC' from 'transformers.models.gpt2.modeling_gpt2' error:

#!/bin/bash

# Use CONDA_PREFIX which points to current active environment
if [ -z "$CONDA_PREFIX" ]; then
    echo "Error: No conda environment is currently active"
    exit 1
fi

# Comment out all lines in the safe package __init__.py
sed -i 's/^/# /' "$CONDA_PREFIX/lib/python3.10/site-packages/safe/__init__.py"

# Import required packages
echo "from .converter import SAFEConverter, decode, encode" >> "$CONDA_PREFIX/lib/python3.10/site-packages/safe/__init__.py"

echo "Fixed safe package in environment: $CONDA_PREFIX"

Training

We provide the pretrained checkpoint. Place model.ckpt in the current top genmol directory.

(Optional) To train GenMol from scratch, run the following command:

torchrun --nproc_per_node ${num_gpu} scripts/train.py hydra.run.dir=${save_dir} wandb.name=${exp_name}

Other hyperparameters can be adjusted in configs/base.yaml.
The training used 8 NVIDIA A100 GPUs and took ~5 hours.

(Optional) Training with User-defined Dataset

We used the SAFE dataset to train GenMol. To use your own training dataset, first convert your SMILES dataset into SAFE by running the following command:

python scripts/preprocess_data.py ${input_path} ${data_path}

${input_path} is the path to the dataset file with a SMILES in each row. For example,

CCS(=O)(=O)N1CC(CC#N)(n2cc(-c3ncnc4[nH]ccc34)cn2)C1
NS(=O)(=O)c1cc2c(cc1Cl)NC(C1CC3C=CC1C3)NS2(=O)=O
...

${data_path} is the path of the processed dataset.

Then, set data in base.yaml to ${data_path}.

De Novo Generation

Run the following command to perform de novo generation:

python scripts/exps/denovo.py

If you see _pickle.UnpicklingError: invalid load key, '<' error. It is likely coming from /miniconda3/envs/genmol/lib/python3.10/site-packages/tdc/chem_utils/oracle/oracle.py", line 347, in readFragmentScores _fscores = pickle.load(f)

The root cause turned out to be a corrupted or incompletely downloaded pkl file for the SA score. The fix is simple: just grab the correct files from the official RDKit repository: https://github.com/rdkit/rdkit/tree/master/Contrib/SA_Score/fpscores.pkl.gz

Extract the downloaded file into the genmol/oracle directory

The experiment in the paper used 1 NVIDIA A100 GPU.

Fragment-constrained Generation

Run the following command to perform fragment-constrained generation:

python scripts/exps/frag.py

The experiment in the paper used 1 NVIDIA A100 GPU.

Goal-directed Hit Generation (PMO Benchmark)

We provide the fragment vocabularies in the folder scripts/exps/pmo/vocab.

(Optional) Place zinc250k.csv in the data folder, then run the following command to construct the fragment vocabularies and label the molecules with property labels:

python scripts/exps/pmo/get_vocab.py

Run the following command to perform goal-directed hit generation:

python scripts/exps/pmo/run.py -o ${oracle_name}

The generated molecules will be saved in scripts/exps/pmo/main/genmol/results.

Run the following command to evaluate the result:

python scripts/exps/pmo/eval.py ${file_name}
# e.g., python scripts/exps/pmo/eval.py scripts/exps/pmo/main/genmol/results/albuterol_similarity_0.csv

The experiment in the paper used 1 NVIDIA A100 GPU and took ~2-4 hours for each task.

Goal-directed Lead Optimization

Run the following command to perform goal-directed lead optimization:

python scripts/exps/lead/run.py -o ${oracle_name} -i ${start_mol_idx} -d ${sim_threshold}

The generated molecules will be saved in scripts/exps/lead/results.

Run the following command to evaluate the result:

python scripts/exps/lead/eval.py ${file_name}
# e.g., python scripts/exps/lead/eval.py scripts/exps/lead/results/parp1_id0_thr0.4_0.csv

The experiment in the paper used 1 NVIDIA A100 GPU and took ~10 min for each task.

License

Copyright @ 2025, NVIDIA Corporation. All rights reserved.
The source code is made available under Apache-2.0.
The model weights are made available under the NVIDIA Open Model License.

Citation

If you find this repository and our paper useful, we kindly request to cite our work.

@article{lee2025genmol,
  title     = {GenMol: A Drug Discovery Generalist with Discrete Diffusion},
  author    = {Lee, Seul and Kreis, Karsten and Veccham, Srimukh Prasad and Liu, Meng and Reidenbach, Danny and Peng, Yuxing and Paliwal, Saee and Nie, Weili and Vahdat, Arash},
  journal   = {International Conference on Machine Learning},
  year      = {2025}
}