TAS2R Receptor Response Helps Design New Antimicrobial Molecules for the 21st Century

Artificial intelligence (AI) requires the provision of learnable data to successfully deliver requisite prediction power. In this article, it is demonstrable that standard physico-chemical parameters, while useful, are insufficient for the development of powerful antimicrobial prediction algorithms. Initial models that focussed solely on the values extractable from the knowledge on electrotopological, structural and constitutional descriptors did not meet the acceptance criteria for classifying antimicrobial activity. In contrast, efforts to conceptually define the diametric opposite of an antimicrobial compound helped to advance the predicted category as a learnable trait. Remarkably, the inclusion of ligand–receptor interactions using the ability of the molecules to stimulate transmembrane TAS2Rs receptor helped to increase the ability to distinguish the antimicrobial molecules from the inactive ones, confirming the hypothesis of a predictor–predicted synergy behind bitterness psychophysics and antimicrobial activity. Therefore, in a single bio–endogenic psychophysical vector representation, this manuscript helps demonstrate the contribution to parametrization and the identification of relevant chemical manifolds for molecular design and (re-)engineering. This novel approach to the development of AI models accelerated molecular design and facilitated the selection of newer, more powerful antimicrobial agents. This is especially valuable in an age where antimicrobial resistance could be ruinous to modern health systems.