Using deep neural networks to explore chemical space

The popularity and success of advanced AI methods like deep neural networks has led to novel ways for exploring chemical space. Their opaque nature poses challenges for model evaluation regarding novelty, uniqueness, and distribution of the chemical space covered. However, these methods also promise to be able to explore uncharted chemical space in novel ways that do not rely directly on structural similarity.

This review provides an overview of popular deep learning methods for chemical space exploration. Crucial aspects like choice of molecular representation, training for focused chemical space exploration, and criteria for assessing and validating chemical space coverage are discussed.

Deep learning offers great potential for chemical space exploration beyond conventional fragment-based methods. Given the rarity of prospective applications and considering the difficulty in assessing representativeness and comprehensiveness of chemical space covered, developing criteria for assessing and validating generative models is of great significance. Latent space models like variational autoencoders are conceptually appealing for inverse QSAR/QSPR approaches as neighborhood relationships in latent space can be trained to reflect property similarities. Future research in understanding and interpreting generative models might lead to a better understanding of biologically relevant properties of molecules.