The Pocket Around Phe58: No Aromatic Contacts

ESM2 assigns F58I a strongly negative score (log-likelihood −4.70). The structure shows why that prior misses the local context — Phe58 sits in a purely aliphatic pocket with zero pi-stacking or cation-pi interactions.

Protein surface Cartoon backbone Pocket surface Labels

Phe58 (aromatic ring)

Pocket residues (aliphatic)

Protein surface

ML Model Prediction

ESM2 log-likelihood: −4.70
"Phe is highly conserved here. Removing an aromatic ring from the core is always destabilizing."

Structural Reality

Aromatic contacts: 0
No pi-stacking, no cation-pi. The flat ring geometry is suboptimal in this aliphatic pocket. Ile packs better → +6.6°C