Adversarial Learned Molecular Graph Inference and Generation

This is a TensorFlow implementation of ALMGIG – Adversarial Learned Molecular Graph Inference and Generation.

Previous methods for molecular graph generation require solving an expensive graph isomorphism problem during training. ALMGIG is a likelihood-free adversarial learning framework for inference and de novo molecule generation that avoids explicitly computing a reconstruction loss. Our approach extends generative adversarial networks by including an adversarial cycle-consistency loss to implicitly enforce the reconstruction property. To quantify the performance of models, we propose to compute the distance between distributions of physicochemical properties with the 1-Wasserstein distance.

Installation

Docker (Linux only)

1. Install Docker and nvidia-docker.
2. Build Docker image almgig:

cd dockerfiles/
./build-image.sh

3. IMPORTANT: Run all remaining scripts via the run-docker.sh script. For instance, to run python train_and_evaluate.py almgig --help, run

./run-docker.sh python train_and_evaluate.py almgig --help

Manually

1. Download and install Miniconda for Python 3.
2. Create a new conda environment almgig with all dependencies:

conda env create -n almgig --file dockerfiles/requirements.yaml

3. Activate the new environment:

conda activate almgig

4. Manually install GuacaMol without its dependencies:

pip install --no-deps 'guacamol==0.3.2'

5. Create fake fcd module which is imported by guacamol, but we don't use:

mkdir $(conda info --base)/envs/almgig/lib/python3.7/site-packages/fcd
touch $(conda info --base)/envs/almgig/lib/python3.7/site-packages/fcd/__init__.py

Preparing the Data

The experiments in the paper use the GDB-9 dataset with at most 9 heavy atoms. To download and preprocess the data, go to the data directory and execute the get-gdb9.sh script:

cd data/
./get-gdb9.sh

This can take a while. If everything completed successfully, you should see

All files have been created correctly.

Generated splits for training, validation, and testing will be stored in data/gdb9/.

Training ALMGIG

To train ALMGIG with the same set of hyper-parameters as in the paper, run

./train_and_evaluate.sh

The script will save checkpoints in the models/gdb9/almgig/ directory. After training, several files will be generated for validation purposes:

1. Metrics comparing the distribution of 10 physicochemical properties of generated molecules and the training (test) data will be written to outputs/descriptors/train/ (outputs/descriptors/test/).
2. Linear interpolation in latent space of 100 randomly selected pairs of molecules will be stored in outputs/nearest_neighbors/.
3. An interpolation along two dimension of the latent space will be written to outputs/interpolation-test.svg.
4. Statistics on invalid molecules will be written to outputs/errors-table.tex.

If you require more control over training and the architecture, directly call the script train_and_evaluate.py. To see a full list of available options, run

python train_and_evaluate.py almgig --help

To monitor generated molecules and their properties during training, you can use TensorBoard:

tensorboard --logdir models/gdb9/

Training Baseline Models

We trained and validated several baseline models on the same set of molecules as ALMGIG. Details are described in a separate README.

Evaluation

When performing training as above, statistics for each generated molecule will be generated automatically, for other models, you can create a file with generated molecules in SMILES representation (one per line), and execute the following script to compute statistics:

python results/grammarVAE_asses_dist.py \
	--strict \
	--train_smiles data/gdb9/graphs/gdb9_train.smiles \
	-i "molecules-smiles.txt" \
	-o "outputs/other-model-distribution-learning.json"

This will generate outputs/other-model-distribution-learning.json containing simple validation metrics (validity, uniqueness, novelty) as well as outputs/other-model-distribution-learning.csv containing generated molecules.

To compute and compare physicochemical properties of generated molecules, run

python -m gan.plotting.compare_descriptors \
    --dist 'emd' \
    --train_file data/gdb9/graphs/gdb9_test.smiles \
    --predict_file \
    "models/gdb9/almgig/distribution-learning_model.ckpt-51500.csv" \
    "outputs/other-model-distribution-learning.csv" \
    --name "My Model" "Other Model" \
    --palette "stota" \
    -o "outputs/"

For each set of molecules following the --predict_file option, it will generate a histogram showing the distribution of physicochemical properties of generated molecules and the test data and their difference in terms of 1-Wasserstein (EMD) distance in the outputs directory. Moreover, a plot comparing all models in terms of mean negative exponential 1-Wasserstein distance (mEMD) will be available at outputs/comparison_dist_stota.pdf.

Cite

If you use our work, please cite us:

@inproceedings{Poelsterl2020-ALMGIG,
 author = {P{\"{o}}lsterl, Sebastian and Wachinger, Christian},
 title = {Adversarial Learned Molecular Graph Inference and Generation},
 booktitle = {ECML PKDD},
 year = {2020},
 eprint = {1905.10310},
 eprintclass = {cs.LG},
 eprinttype = {arXiv},
}

Acknowledgements

This project contains modified code from the GuacaMol project, see LICENSE.GUACAMOL for license information.