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Time-resolved HT-SAXS discovers allosteric chemotypes for redox target AIF

We present a discovery pipeline integrating chemical fragment screening and time-resolved, high-throughput small-angle X-ray scattering (TR-HT-SAXS). This approach identifies allosteric chemical leads targeting distinct allosteric states of the mitochondrial oxidoreductase apoptosis-inducing factor (AIF). By monitoring kinetic rates of allosteric transition with TR-HT-SAXS, we link fragment structure–activity relationships (SARs) to biomolecular conformation.

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Fig. 1: TR-HT-SAXS workflow and similarity analysis.


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This is a summary of: Brosey, C. A. et al. Chemical screening by time-resolved X-ray scattering to discover allosteric probes. Nat. Chem. Biol. (2024).

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Time-resolved HT-SAXS discovers allosteric chemotypes for redox target AIF. Nat Chem Biol (2024).

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