ProtAgent: Post-Training Compact Protein Tool Agents with Interaction-Level Credit Assignment

Recent efforts to scale tool-use post-training have largely centered on the synthesis of executable environments, which constitute only one component of a broader agentic interaction system comprising the environment, task, agent harness, and evaluator. Scaling environments in isolation, however, does not guarantee commensurate gains in model performance, because reliable learning signals depend on coherent interactions among all components of the agentic interaction system. To address this problem, we introduce WEFT (Whole-system Evolution For Tool-use Post-training), which couples scalable agentic interaction system construction, execution-driven self-evolution, and stable post-training. WEFT scales agentic interaction system construction across environment breadth, task complexity, and interaction diversity. Execution-driven self-evolution iteratively uses execution traces and state evidence to attribute failures and revise the responsible components, with fresh rollouts evaluating the changes and providing evidence for subsequent evolution rounds. For stable post-training at scale, WEFT addresses both optimization and execution reliability: prefix-preserving sampling retains verified progress and atomic-turn credit assignment localizes learning signals, while MegaMCP maintains isolated, recoverable state across concurrent rollouts over shared tool services. Extensive experiments across various models and benchmarks demonstrate the effectiveness of WEFT for tool-use post-training. WEFT-8B and WEFT-14B outperform all evaluated matched-size environment-scaling baselines on BFCL V4, $τ^2$-Bench, and Claw-Eval. In particular, WEFT-14B improves over Agent-World-14B by 6.41, 2.23, and 12.27 percentage points. WEFT-35B-A3B further extends these gains to more challenging long-horizon workflow benchmarks, including Toolathlon-Verified and AutomationBench.

Large language models (LLMs) are increasingly expected to orchestrate diverse tools over long-horizon tasks. Existing agents typically use Direct Tool Calling (DTC), where the model invokes tools sequentially, and tool responses accumulate in the model context, which can lead to context rot and orchestration breakdown. In contrast, Programmatic Tool Calling (PTC) invokes tools through executable code and stores intermediate results in runtime variables rather than appending them to the context. Prior work has explored PTC mainly as an inference-time optimization, but its benefits for agentic training remain unclear, and suitable verifiable training tasks are scarce. In this work, we introduce ProgAgent, a full PTC training stack, comprising a pipeline for synthesizing verifiable long-horizon tasks, a lightweight PTC runtime, and a two-stage training recipe. Using only 215 tasks instantiated at four environment scales, ProgAgent yields higher pass rates than the evaluated baselines of comparable size across four benchmarks. On LOCA-bench, ProgAgent-14B achieves a 30.7% pass rate at a 64k-token environment state, where these baselines score zero. Cross-harness experiments show that PTC-trained models outperform DTC-trained models under both evaluation interfaces, suggesting that the benefits of PTC training extend beyond the interface.

Protein analysis tasks arising in healthcare settings often require accurate reasoning under protein sequence constraints, involving tasks such as functional interpretation of disease-related variants, protein-level analysis for clinical research, and similar scenarios. To address such tasks, search agents are introduced to search protein-related information, providing support for disease-related variant analysis and protein function reasoning in protein-centric inference. However, such search agents are mostly limited to single-round, text-only modality search, which prevents the protein sequence modality from being incorporated as a multimodal input into the search decision-making process. Meanwhile, their reliance on reinforcement learning (RL) supervision that focuses solely on the final answer results in a lack of search process constraints, making deviations in keyword selection and reasoning directions difficult to identify and correct in a timely manner. To address these limitations, we propose ProtRLSearch, a multi-round protein search agent trained with multi-dimensional reward based RL, which jointly leverages protein sequence and text as multimodal inputs during real-time search to produce high quality reports. To evaluate the ability of models to integrate protein sequence information and text-based multimodal inputs in realistic protein query settings, we construct ProtMCQs, a benchmark of 3,000 multiple choice questions (MCQs) organized into three difficulty levels. The benchmark evaluates protein query tasks that range from sequence constrained reasoning about protein function and phenotype changes to comprehensive protein reasoning that integrates multi-dimensional sequence features with signal pathways and regulatory networks.