Beyond Affinity: A Benchmark of 1D, 2D, and 3D Methods Reveals Critical Trade-offs in Structure-Based Drug Design

This repository hosts an open-source benchmark for Structure-based Drug Design, to facilitate the transparent and reproducible evaluation of algorithmic advances in molecular optimization. This repository supports 15 Structure-based Drug Design algorithms on 4 tasks categories.

15 Methods

Model	Dimension	Tested molcules (Avg)	requires_gpu
3DSBDD	3D	771	yes
Pocket2mol	3D	928	yes
PocketFlow	3D	1000	yes
RenGen	3D	631	yes
DST	2D	1001	no
Graph GA	2D	643	no
MIMOSA	2D	1001	yes
MolDQN	2D	501	yes
Pasithea	1D	914	yes
REINVENT	1D	1000	yes
SELFIES-VAE-BO	1D	200	yes
SMILES-GA	1D	584	no
SMILES-LSTM-HC	1D	501	no
SMILES-VAE-BO	1D	200	yes
TargetDiff	3D	75	yes

Receptor information

All the receptors used in our benchmark can be found in receptor/ folder

Sampling and evaluating

For 3DSBDD and Pocket2mol, we use this command to generate:

python sample_for_pdb.py --pdb_path [your pdb] --center=[centers] --bbox_size [box size] --outdir [your outdir]

Also need to change the num_samples in the sample_for_pdb.yml

For PocketFlow, we use this command to generate:

python main_generate.py -pkt [your pdb] --ckpt ckpt/ZINC-pretrained-255000.pt -n 1000 -d cuda:0 --root_path [your outdir] --name [pdb name] -at 1.0 -bt 1.0 --max_atom_num 35 -ft 0.5 -cm True --with_print True

For ResGen, we first convert our pdb file to sdf file and use this command to generate:

python gen.py --pdb_file [your pdb] --sdf_file [correspond sdf] --outdir [your outdir]

For the rest of models that are under PMO, we use the following command to generate

python -u run.py --method [method to test] --task production --n_runs 3 --wandb offline --max_oracle_calls 5 --custom_docking [your pdb] --custom_docking_config [your pdb config]

After getting molecules, we could start evaluate. First we calculate the docking score using vina_test_model_pmo.py or vina_test_model_pmo.py. Then we could run Heuristic Oracles and Molecule Generation Oracles using heuristic_merics.py and generation_metrics.py. At last we could run pose test with posebuster_test.py and clash_test.py

Environment

To run vina, please use vina_environment

To run Heuristic Oracles and Molecule Generation Oracles, please use pyscreener_environment

To run pose test, please use posebusters_environment