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Spatial Graph Attention and Curiosity-driven Policy for Antiviral Drug Discovery

Yulun Wu · Nicholas Choma · Andrew Chen · Mikaela Cashman · Erica Teixeira Prates · Veronica Melesse Vergara · Manesh Shah · Austin Clyde · Thomas Brettin · Wibe de Jong · Neeraj Kumar · Martha Head · Rick Stevens · Peter Nugent · Daniel Jacobson · James Brown

Keywords: [ reinforcement learning ] [ graph neural network ] [ drug discovery ]


We developed Distilled Graph Attention Policy Networks (DGAPNs), a reinforcement learning model to generate novel graph-structured chemical representations that optimize user-defined objectives by efficiently navigating a physically constrained domain. The framework is examined on the task of generating molecules that are designed to bind, noncovalently, to functional sites of SARS-CoV-2 proteins. We present a spatial Graph Attention (sGAT) mechanism that leverages self-attention over both node and edge attributes as well as encoding the spatial structure --- this capability is of considerable interest in synthetic biology and drug discovery. An attentional policy network is introduced to learn the decision rules for a dynamic, fragment-based chemical environment, and state-of-the-art policy gradient techniques are employed to train the network with stability. Exploration is driven by the stochasticity of the action space design and the innovation reward bonuses learned and proposed by random network distillation. In experiments, our framework achieved outstanding results compared to state-of-the-art algorithms, while reducing the complexity of paths to chemical synthesis.

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