Self-Improvement Imitation with Biologically Guided Search for Protein Design Under Oracle Budgets 文章

arXiv:2605.26690v1 Announce Type: cross Abstract: Protein sequence optimization under tight oracle budgets requires methods that explore vast combinatorial spaces while making each evaluation informative. Existing reinforcement learning and off-policy generative approaches often degrade under surrogate noise, and position-agnostic mutation proposals risk disrupting functionally critical residues. We introduce SILO, a trajectory-level self-improvement imitation framework for oracle-budgeted protein design. SILO uses a hierarchical edit policy that decomposes each mutation into a position choice followed by a residue choice. In each active-learning round, the policy samples candidate trajectories via incremental stochastic beam search without replacement (SBS), and a UCB-based proxy ensemble, combined with an alanine-scan fitness score (AFS), selects candidates with functionally relevant edits for in silico oracle evaluation.