Variational autoencoder-based chemical latent space for large molecular structures with 3D complexity.

The structural diversity of chemical libraries, which are systematic collections of compounds that have potential to bind to biomolecules, can be represented by chemical latent space. A chemical latent space is a projection of a compound structure into a mathematical space based on several molecular features, and it can express structural diversity within a compound library in order to explore a broader chemical space and generate novel compound structures for drug candidates. In this study, we developed a deep-learning method, called NP-VAE (Natural Product-oriented Variational Autoencoder), based on variational autoencoder for managing hard-to-analyze datasets from DrugBank and large molecular structures such as natural compounds with chirality, an essential factor in the 3D complexity of compounds. NP-VAE was successful in constructing the chemical latent space from large-sized compounds that were unable to be handled in existing methods, achieving higher reconstruction accuracy, and demonstrating stable performance as a generative model across various indices. Furthermore, by exploring the acquired latent space, we succeeded in comprehensively analyzing a compound library containing natural compounds and generating novel compound structures with optimized functions.

The Stroop effect involves an excitatory-inhibitory fronto-cerebellar loop.

The Stroop effect is a classical, well-known behavioral phenomenon in humans that refers to robust interference between language and color information. It remains unclear, however, when the interference occurs and how it is resolved in the brain. Here we show that the Stroop effect occurs during perception of color-word stimuli and involves a cross-hemispheric, excitatory-inhibitory loop functionally connecting the lateral prefrontal cortex and cerebellum. Participants performed a Stroop task and a non-verbal control task (which we term the Swimmy task), and made a response vocally or manually. The Stroop effect involved the lateral prefrontal cortex in the left hemisphere and the cerebellum in the right hemisphere, independently of the response type; such lateralization was absent during the Swimmy task, however. Moreover, the prefrontal cortex amplified cerebellar activity, whereas the cerebellum suppressed prefrontal activity. This fronto-cerebellar loop may implement language and cognitive systems that enable goal-directed behavior during perceptual conflicts.