Miriam Poley-Gil

The paper investigates whether functional frustration in proteins is an evolutionary adaptation or a byproduct of fold architecture, finding that frustration hotspots are inherent physical constraints co-opted for function.

A fine-tuned ProtT5 protein language model predicts per-residue energetic frustration from sequence (Pearson r 0.86 on unseen CATH topologies) and profiles the human proteome in ~17 minutes on one GPU.

FrustraEvo calculates and quantifies the conservation of local energetic frustration in protein families to identify evolutionary stability and functional constraints.