Exploring the potential of AlphaFold distograms for predicting binding‐induced hinge motions
Year: 2026
Type: article
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 hinge regions in cryo-EM maps. Impact statement We reveal that AlphaFold distograms can successfully predict binding-induced hinge motions. This establishes distograms as a valuable, structure-free metric for identifying alternative conformational states, aiding the interpretation of ambiguous densities in cryo-EM maps.
Source: FEBS Letters
Authors: Büşra Savaş, Ayşe Berçin Barlas, Ezgi Karaca
Institutions: Dokuz Eylül University, Izmir Biomedicine and Genome Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W7127579793