How to Spend Your Oracle Budget: Practical Guidance for Protein Structure Prediction Models

TL;DR - This study benchmarks oracle-budget-aware guidance methods for protein structure prediction. It finds that method effectiveness depends on budget: O3 performs best at low budgets, while FK-steering and DPO improve as budgets grow.

• Compares O3, FK-steering, DPO, and Best K-of-N sampling under constrained oracle access.
• Extends Optimisation Over Outputs (O3) to protein structure prediction models.
• Evaluates guidance on calmodulin (1CLL) and E. coli aspartate transcarbamoylase (9EEH).
• Provides practical method-selection recommendations rather than identifying one universally dominant approach.