Profiling Chemobiological Connection between Natural Prod-uct and Target Space Based on Systematic Analysis

Natural products provides valuable starting points for new drugs with unique chemical structures. Here we retrieve and join LOTUS natural product database and ChEMBL interaction database to explore the relations and rhythm between chemical features of natural products and biotarget spaces. Our analysis revealed relations between the biogenic pathways of natural products and species taxonomy. The data analysis revealed that the N atom was the privileged structure of a highly active natural product. An apparent trend exists in the target space of natural products originating from different biological sources. Alkaloids focused on neurological effects. Oligopeptides and polyketides were mainly associated with protein phosphorylation and HDAC receptors. Fatty acids readily intervene in various physiological processes involving Prostanoids and Leukotrienes. We also used FusionDTA, a deep learning model, to predict the affinity between all LOTUS natural products and 622 therapeutic drug targets, exploring the potential target space for natural products. Our data exploration provided a global perspective on the gaps in the chemobiological space of natural compounds through systematic analysis and prediction of their target space, which can be used for new drug design or natural drug repurposing.