Facilitating the identification of cryo-EM hit matter in drug discovery with Astex-Faro

Astex-Faro detects subtle structural deviations in cryo-EM target maps and enhances weak or partially occupied features, using Fourier Shell Coherence (FSCoh) to quantify ensemble consistency.

• Why it matters: Cryo-EM ligand and fragment screening produces large reconstruction collections, but local density variations—especially weak or poorly resolved features—are hard to interpret and can be missed.
• What they did: The framework defines an expected specimen state from a reference ensemble, compares it to a target map to flag significant deviations, and introduces FSCoh to measure consistency across reconstruction ensembles.
• The result: Across datasets spanning highly homogeneous specimens, membrane proteins, low-occupancy ligands, and fragment-screening experiments, it reliably detects subtle features and improves interpretability, supporting more confident hit identification.

AI summary of the abstract · may contain errors · not medical advice · read the paper.