Exploring the potential of AlphaFold distograms for predicting binding-induced hinge motions
FEBS Letters, vol.600, no.10, pp.1558-1570, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 600 Issue: 10
- Publication Date: 2026
- Doi Number: 10.1002/1873-3468.70297
- Journal Name: FEBS Letters
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE
- Page Numbers: pp.1558-1570
- Keywords: AlphaFold, binding-induced hinge motion, conformational flexibility, distogram, multiple sequence alignment
- Dokuz Eylül University Affiliated: Yes
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.