Bridging the Evidence-to-Execution Gap:A Reflective Agent for Multi-Objective Peptide Design

원문 초록

Large language models can reason over scientific literature, but textual plans do not reliably produce biological sequences with the intended properties. Sequence generators capture sequence patterns, yet they do not interpret evidence, choose interventions, or reflect on outcomes. This separation creates an evidence-to-execution gap between scientific reasoning and sequence-level control. We introduce EASER, a reflective agent that connects the two through a learned property interface. The interface consists of property-specific low-rank directions trained offline and fixed during search; an LLM controller (the controller) composes them to steer a frozen diffusion generator. From retrieved evidence, sequence context, and prior outcomes, it proposes intervention hypotheses that specify anchors, editable positions, and coefficients. Probe-and-Steer tests these hypotheses and allocates further samples from their joint predicted responses; reflection updates the agent's memory. On computational antimicrobial peptide design, EASER balances activity, non-hemolysis, and non-toxicity. Explicit hypothesis formulation yields larger multi-objective gains than direct action generation, and ablations support evidence retrieval, episodic history, reflection, and Probe-and-Steer. EASER achieves the highest mean hypervolume and lowest mean IGD+ among the evaluated search policies and generators on screened candidates. These results show that a learned property interface can make literature-grounded reasoning executable at the sequence level.