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bioRxiv · 10.1101/2025.07.25.666757

Exploring the Potential of AlphaFold Distograms for Flexibility Assignment in Cryo-EM Maps

Savas, B.·Barlas, A. B.·Karaca, E.
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Abstract

AlphaFold models provide static structural predictions, limiting their use in interpreting flexible regions in low-resolution cryo-EM maps. Here, we assess whether AlphaFold-generated distograms can instead reveal conformational flexibility, focusing on binding-induced hinge motions. For this, we examined the key metabolic AK2/AIFM1 complex, where molecular dynamics and cryo-EM confirm a hinge motion in AK2 upon binding. Notably, this motion is captured in the AlphaFold2/3 distograms of apo AK2, even though it is absent in the predicted structures. By extending our analysis to other systems, we demonstrate that distograms may offer a valuable, model-independent method for interpreting ambiguous regions in cryo-EM maps.

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Savas, B., Barlas, A. B., Karaca, E.. 2025-07-27. Exploring the Potential of AlphaFold Distograms for Flexibility Assignment in Cryo-EM Maps. https://doi.org/10.1101/2025.07.25.666757

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