MolecularRNN: Generating realistic molecular graphs with optimized properties
This addresses the need for de-novo molecular design in drug discovery, representing a strong specific gain with competitive benchmarks.
The authors tackled the problem of generating new molecules with specific properties for drug discovery by developing MolecularRNN, a graph recurrent generative model that, after pretraining and tuning with policy gradient, significantly shifted distributions toward desired ranges for properties like lipophilicity and achieved 100% validity with rejection sampling.
Designing new molecules with a set of predefined properties is a core problem in modern drug discovery and development. There is a growing need for de-novo design methods that would address this problem. We present MolecularRNN, the graph recurrent generative model for molecular structures. Our model generates diverse realistic molecular graphs after likelihood pretraining on a big database of molecules. We perform an analysis of our pretrained models on large-scale generated datasets of 1 million samples. Further, the model is tuned with policy gradient algorithm, provided a critic that estimates the reward for the property of interest. We show a significant distribution shift to the desired range for lipophilicity, drug-likeness, and melting point outperforming state-of-the-art works. With the use of rejection sampling based on valency constraints, our model yields 100% validity. Moreover, we show that invalid molecules provide a rich signal to the model through the use of structure penalty in our reinforcement learning pipeline.