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Paper · 2310.03223 · 2023

TacoGFN: Target-conditioned GFlowNet for Structure-based Drug Design

arXiv · PDF · Open in the Atlas

Code that ran

We lifted 10 functions out of this paper's own repositories and ran 6 of them in a sandbox. "Ran" means the function executed on a synthesized input and returned a value. It is not a reproduction of the paper's results.

RepositoryRoleRan
tsa87/TacoGFN-SBDD canonical 5 of 9
copy not recorded — 1 of 1
FunctionStatusWhere it lives
safe Ran this paper's copy was not recorded; identical code first harvested from SeonghwanSeo/RxnFlow
pointer only · get_code("1061c8464b631df1")
cross Ran tsa87/TacoGFN-SBDD/src/tacogfn/algo/trajectory_balance.py
code served (permissive licence) · get_code("2a8ed5bf472b7004")
graph_without_edge Ran tsa87/TacoGFN-SBDD/src/tacogfn/envs/graph_building_env.py
code served (permissive licence) · get_code("698d73f4260ce129")
graph_without_node Ran tsa87/TacoGFN-SBDD/src/tacogfn/envs/graph_building_env.py
code served (permissive licence) · get_code("91084575c9dd054e")
graph_without_node_attr Ran tsa87/TacoGFN-SBDD/src/tacogfn/envs/graph_building_env.py
code served (permissive licence) · get_code("cf0b5b8b09080022")
shift_right Ran tsa87/TacoGFN-SBDD/src/tacogfn/algo/trajectory_balance.py
code served (permissive licence) · get_code("a508d01ed77ced0b")
compute_docking_score_from_pdbqt Not yet run tsa87/TacoGFN-SBDD/src/tacogfn/eval/docking.py
code served (permissive licence) · get_code("e250ae2890e72adb")
load_original_model Not yet run tsa87/TacoGFN-SBDD/src/tacogfn/models/bengio2021flow.py
code served (permissive licence) · get_code("6f8307be25b9b963")
load_weights Not yet run tsa87/TacoGFN-SBDD/src/tacogfn/models/bengio2021flow.py
code served (permissive licence) · get_code("23e26258a406f7d5")
subTB Not yet run tsa87/TacoGFN-SBDD/src/tacogfn/algo/trajectory_balance.py
code served (permissive licence) · get_code("3215acf27eba4238")

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Abstract

Searching the vast chemical space for drug-like molecules that bind with a protein pocket is a challenging task in drug discovery. Recently, structure-based generative models have been introduced which promise to be more efficient by learning to generate molecules for any given protein structure. However, since they learn the distribution of a limited protein-ligand complex dataset, structure-based methods do not yet outperform optimization-based methods that generate binding molecules for just one pocket. To overcome limitations on data while leveraging learning across protein targets, we choose to model the reward distribution conditioned on pocket structure, instead of the training data distribution. We design TacoGFN, a novel GFlowNet-based approach for structure-based drug design, which can generate molecules conditioned on any protein pocket structure with probabilities proportional to its affinity and property rewards. In the generative setting for CrossDocked2020 benchmark, TacoGFN attains a state-of-the-art success rate of $56.0\%$ and $-8.44$ kcal/mol in median Vina Dock score while improving the generation time by multiple orders of magnitude. Fine-tuning TacoGFN further improves the median Vina Dock score to $-10.93$ kcal/mol and the success rate to $88.8\%$, outperforming all optimization-based methods.

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