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Phys.org — Biology · September 7, 2026

Breaking through AlphaFold's limits to predict how proteins change shape

BiologyChemistryComputer Science
THE AI ANGLE
Sampling dynamic protein conformations using biased diffusion generative models

Researchers developed AF3-ReD, a technique that introduces a repulsive bias into AlphaFold3's diffusion generative model to steer it away from previously generated structures. While standard AlphaFold3 typically predicts only a single low-energy conformation, this method successfully samples multiple conformational states, such as the open, closed, and intermediate forms of ATP synthase's F1β subunit. This advancement enables rapid prediction of dynamic protein shape changes, which are vital for biological function and targeted drug design.

THE TEACHING ANGLE
Instructors can explore how AlphaFold3's diffusion model inherently converges on a single lowest-energy state and how introducing an artificial repulsive bias overcomes this limitation to model dynamic conformational ensembles.

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