For unconditional design, we get high-pLDDT proteins unlike any known sequences. A small TEA k-mer diversity loss helped steer us away from simple coiled-coils toward complex secondary structure combos. (6/n)

For template-guided design, we generated novel sequences predicted to fold into both de novo and natural scaffolds (AF2 single seq). Many have a NEFF of 1. No structures were used in the making of these designs. (5/n)

The approach:
1. Take a random sequence
2. Randomly mutate
3. Accept/reject via Metropolis criterion based on ESM2 likelihood + TEA template match (or TEA entropy if unconditional).
This is fast, 30k steps in ~25min. (4/n)

@jeeberhardt.bsky.social presenting CASP16 PLI baselines. Big shout out to @jeremywohlwend.bsky.social and @gcorso.bsky.social for helping us with running Boltz-1 on short notice! Pretty weird results on autotaxin.

@peterskrinjar.bsky.social presenting #CAMEO and #PLINDER at #CASP16 , i.e what we at the @torstenschwede.bsky.social group have been up to since last CASP in automating benchmarking of complex prediction.