Digital annealing optimization for natural product structure elucidation

Abstract The digital annealer (DA) leverages its computational capabilities of up to 100 000 bits to address the complex nondeterministic polynomial-time (NP)-complete challenge inherent in elucidating complex structures of natural products. Conventional computational methods often face limitations with complex mixtures, as they struggle to manage the high dimensionality and intertwined relationships typical in natural products, resulting in inefficiencies and inaccuracies. This study reformulates the challenge into a Quadratic Unconstrained Binary Optimization framework, thereby harnessing the quantum-inspired computing power of the DA. Utilizing mass spectrometry data from three distinct herb species and various potential scaffolds, the DA proficiently locates optimal sidechain combinations that adhere to predefined target molecular weights. This methodology enhances the probability of selecting appropriate sidechains and substituted positions and ensures the generation of solutions within a reasonable 5-min window. The findings underscore the transformative potential of the DA in the realms of analytical chemistry and drug discovery, markedly improving both the precision and practicality of natural product structure elucidation. Graphical Abstract Graphical Abstract