Constraint-Aware Corrective Memory for Language-Based Drug Discovery Agents

Building state-of-the-art (SOTA) predictive models for drug discovery requires expensive search over tools, architectures, and training strategies. Current LLM-based agents can find SOTA solutions through extensive trial and error, but they do not retain the experience accumulated along the way and therefore pay the full search cost on every new task. We propose \method (Self-evolving Agent Experience), a framework that accumulates and reuses experience across tasks to build SOTA drug discovery models efficiently. \method maintains a cross-task memory of verified skills, statistical evidence about effective strategies, and a record of recurring errors and their fixes. In some cases, \method transfers a working solution directly without test-time search. In 33 molecular property prediction tasks, \method ranks first among nine SOTA agents in a single-task setting. With memory accumulated from 16 smaller tasks, \method achieves an averaged normalized score of 0.935 on 17 held-out tasks in a cross-task evaluation setting and outperforms all baseline agents by 10-30% in a zero-test-time search regime. In summary, our work shows the advantage of cross-task memory for efficient SOTA model development in drug discovery.

Drug discovery remains a resource-intensive and time-consuming process, involving billions of dollars and a decade of development to advance a drug to market. While many in silico tools have accelerated this process, operating them still demands substantial time, effort, and expertise from medicinal chemists. Autonomous systems built on Large Language Models (LLMs) have emerged as a promising solution, yet current designs limit their performance. Existing single-agent systems scale poorly to long-horizon, multi-step, and realistic tasks, whereas multi-agent systems typically execute predefined workflows that cannot capture the iterative, non-linear nature of a real drug discovery campaign. Here, we present MADDIE, a multi-agent drug discovery engine. It comprises a central agent, Orchestrator, and four specialized worker agents: HitIdentifier, LeadOptimizer, Synthesizer, and Evaluator, each representing a critical step in a drug discovery campaign. Under Orchestrator's orchestration and coordination, these worker agents are composed into flexible workflows, enabling MADDIE to adapt its strategy and navigate the drug discovery pipeline end-to-end. Across 50 protein targets, MADDIE produces molecules satisfying key property requirements and their synthesis routes, outperforming existing agentic systems, generative models, and general-purpose LLMs by a wide margin. Our analysis reveals how these agents collaborate and that MADDIE can employ different strategies across targets to achieve the campaign's goal, while still being efficient in time and tokens. Together, they demonstrate MADDIE as a low-cost, effective, and efficient autonomous engine for accelerating drug discovery. Code and dataset is available via https://github.com/ninglab/MADDIE.

Tool-augmented large language model (LLM) agents promise to unify scientific reasoning with computation, yet their deployment in high-stakes domains like drug discovery is bottlenecked by two critical barriers: unconstrained tool-use governance and poor long-horizon reliability. In dependency-heavy pharmaceutical pipelines, autonomous agents often drift into irreproducible trajectories, where early-stage hallucinations multiplicatively compound into downstream failures. To overcome this, we present Mozi, a dual-layer architecture that bridges the flexibility of generative AI with the deterministic rigor of computational biology. Layer A (Control Plane) establishes a governed supervisor--worker hierarchy that enforces role-based tool isolation, limits execution to constrained action spaces, and drives reflection-based replanning. Layer B (Workflow Plane) operationalizes canonical drug discovery stages -- from Target Identification to Lead Optimization -- as stateful, composable skill graphs. This layer integrates strict data contracts and strategic human-in-the-loop (HITL) checkpoints to safeguard scientific validity at high-uncertainty decision boundaries. Operating on the design principle of ``free-form reasoning for safe tasks, structured execution for long-horizon pipelines,'' Mozi provides built-in robustness mechanisms and trace-level audibility to completely mitigate error accumulation. We evaluate Mozi on PharmaBench, a curated benchmark for biomedical agents, demonstrating superior orchestration accuracy over existing baselines. Furthermore, through end-to-end therapeutic case studies, we demonstrate Mozi's ability to navigate massive chemical spaces, enforce stringent toxicity filters, and generate highly competitive in silico candidates, effectively transforming the LLM from a fragile conversationalist into a reliable, governed co-scientist.