AlphaUnfold: Probing Potential Unfolding and Structural Fragility in AlphaFold3 Models via Short-Time High-Pressure MD (opens in new tab)

We developed AlphaUnfold, an automated pipeline that couples AF3 predictions with short-time (5 ns) high-pressure Molecular Dynamics (MD) using NAMD3. By subjecting models to baric stress, AlphaUnfold acts as a dynamic stress-test to identify structural fragility and potential unfolding. Testing a diverse set of proteins revealed a significant inverse correlation between average pLDDT and Root Mean Square Deviation (RMSD) after MD, indicating that lower confidence translates to rapid structur...