Finding and targeting cryptic pockets could dramatically expand the druggable proteome. However, discovering these sites remains challenging since they are only open a fraction of the time. It is also difficult to predict the functional relevance of a cryptic site as this often requires insight into allostery. Here we introduce attention enabled (AE-)PocketMiner, an artificial intelligence (AI) method that uses a graph neural network with an attention mechanism to simultaneously predict the locations of cryptic pockets and their allosteric coupling to the rest of the protein from a single input structure. We show that AE-PocketMiner outperforms past methods for identifying cryptic pockets and recapitulates known allosteric interactions. Moreover, we experimentally confirm newly predicted cryptic pockets and mutations that allosterically control pocket opening. AE-PocketMiner thus provides a powerful framework for multiple steps of the drug discovery process–including pocket identification, prioritization, and assay design–that will help expand the druggable proteome.
Crisis support teams’ technological openness and learning attitudes toward the AI based virtual patient system crisis support VR
BackgroundAgainst the backdrop of escalating global humanitarian crises, innovative didactic simulations are becoming increasingly important. A promising alternative to traditional classroom-based didactics for learning psychological