Enhancing simulations of disordered protein ensembles with chemical shift restraints in coarse-grained models.

Chemical shift restraints integrated into coarse-grained models enable accurate sampling of secondary structures in IDPs, matching experimental data.

• Why it matters: Understanding the dynamic conformational ensembles of intrinsically disordered proteins (IDPs) is crucial for elucidating their cellular functions, but conventional techniques struggle to capture transient structures at residue resolution.
• What they did: A neural network predicting backbone chemical shifts from C α -only conformations was used to enhance one bead-per-amino acid CG force fields, applied to a large set of IDPs in isolation and condensates.
• The result: The approach accurately recapitulates local and global arrangements, producing ensembles that inform structure-function relationships and address force field limitations in IDP simulations.