Iterative Modeling via Structural Diffusion (IMSD): Exploring Fold-Switching Pathways in Metamorphic Proteins Using AlphaFold2-Based Generative Diffusion Model UFConf.

ABSTRACT: Metamorphic proteins (MPs) can fold into two or more distinct spatial structures. Increasing interest in MPs has spurred the search for computational tools to predict proteins fold-switching potential and model their refolding pathways. Here we address this problem by using the recently reported generative diffusion predictor UFConf, based on the AlphaFold2 network. We have developed a new UFConf-driven algorithm dubbed IMSD (iterative modeling via structural diffusion) to model the MP's path from one conformational state to another. In brief, we begin with the experimental structure of state A, perturb it through the "noising" process, and infer a number of models (replicas) through the reverse diffusion or "denoising" process. From this set of models, we choose the one that is closest to

SUBMITTER: Luzik DA 

PROVIDER: S-EPMC12779232 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature