Exploring the potential of AlphaFold distograms for predicting binding‐induced hinge motions

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.