1. Data-driven discovery of potent small molecule ice recrystallisation inhibitors.
- Author
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Warren, Matthew T., Biggs, Caroline I., Bissoyi, Akalabya, Gibson, Matthew I., and Sosso, Gabriele C.
- Subjects
ICE formation & growth ,MACHINE learning ,ICE prevention & control ,ERYTHROCYTES ,CHEMICAL libraries ,CRYOPROTECTIVE agents - Abstract
Controlling the formation and growth of ice is essential to successfully cryopreserve cells, tissues and biologics. Current efforts to identify materials capable of modulating ice growth are guided by iterative changes and human intuition, with a major focus on proteins and polymers. With limited data, the discovery pipeline is constrained by a poor understanding of the mechanisms and the underlying structure-activity relationships. In this work, this barrier is overcome by constructing machine learning models capable of predicting the ice recrystallisation inhibition activity of small molecules. We generate a new dataset via experimental measurements of ice growth, then harness predictive models combining state-of-the-art descriptors with domain-specific features derived from molecular simulations. The models accurately identify potent small molecule ice recrystallisation inhibitors within a commercial compound library. Identified hits can also mitigate cellular damage during transient warming events in cryopreserved red blood cells, demonstrating how data-driven approaches can be used to discover innovative cryoprotectants and enable next-generation cryopreservation solutions for the cold chain. Controlling ice formation is crucial for cryopreservation. Here, authors developed machine learning models to predict ice recrystallisation inhibition by small molecules, showcasing a data-driven approach for cryoprotectant discovery. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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