Designing a Robust LLM-Based Evaluation System for Agentic AI in Drug Discovery Through Human Alignment

As agentic systems tackle increasingly complex multi-step tasks, evaluating their trajectories presents a major bottleneck - human annotation of a single trajectory on popular agentic benchmarks can take hours, making it difficult to scale evaluations for measuring performance or curating training data. This has driven widespread reliance on automated approaches such as LLM-as-a-judge (LLMJ) to critique agents at the process and outcome-levels at scale, however, the soundness of LLMJ critiques often goes unmeasured. Here, we introduce Counsel, the first public dataset of meta-evaluations for agentic tasks. Counsel consists of process-level critiques from open-weight LLMJs on two agent benchmarks: tau-bench (customer support agents) and DA-Code (coding agents), and human meta-evaluations of these critiques. Human annotators label critiques on each flagged error as "spot on", "correct location but poor reasoning", or "should not have flagged", achieving reliable inter-annotator agreement (Krippendorff's alpha of 0.78). The resulting dataset stratifies LLMJ critiques by human alignment across both error location within a trajectory and reasoning quality, serving as valuable data to calibrate, improve, or train LLMJs for agents. Comparing open-weight judges, we find that more capable judge models and more reasoning effort both enabled improved human agreement, with the strongest judge reaching ~88% agreement on location and ~65% on reasoning. Counsel is generated using open-weight models and is permissively licensed for broad community use, which we hope will enable rigorous study and improved alignment of LLM-based evaluators for agentic systems.

LLM agents have incredible potential for scientific discovery applications. However, the performance of LLM agents on real-world, small molecule drug design (SMDD) tasks across diverse chemistries and targets is unclear. Current evaluation methods are either ad hoc, too simple for real-world discovery, limited in scale, or restricted to single-turn question answering. In effort to standardize the evaluation of LLM agents on small molecule design, we introduce SMDD-Bench, a challenging, multi-turn, long-horizon agentic benchmark consisting of 502 guaranteed-solvable task instances spanning 5 task types: 2D Pharmacophore Identification, Interaction Point Discovery, Scaffold Hopping, Lead Optimization, and Fragment Assembly. SMDD-Bench tasks span a wide region of chemical space and involve 102 unique protein targets. Completely solving the benchmark would require having strong chemical and biological reasoning and 3D intuition, understanding specialized tool use, and displaying planning expertise over a limited number of oracle calls. We benchmark 7 frontier open and closed source LLMs and find even the most performant LLM, GPT5.4, solves only 40.2% of tasks. We hope SMDD-Bench provides a standardized testbed to invigorate the field towards training and evaluating LLM agents for fully autonomous computational drug design. We host a public leaderboard at smddbench.com .

LLM systems for scientific discovery increasingly assist with ideation, literature synthesis, experiment planning, and report generation, but the first research question they propose can remain difficult to audit: it may sound plausible without exposing the mechanism, falsifier, or assumption that a scientist should inspect. We introduce FirstResearch, a first-principles research-question formation framework for scientific LLM agents whose core artifact is a structured Research Question Certificate. The certificate records primitive definitions, assumptions, a mechanism model, a tension or contradiction, a falsifiable hypothesis, a minimal decisive test, and a failure update rule, making the proposed question inspectable before downstream execution. On ten LLM-agent research topics, FirstResearch outperforms controlled prompt-level baselines inspired by AI co-scientist, Agent Laboratory, and AI Scientist-v2 under a primary DeepSeek-blind-judge protocol. A Gemini-2.5-Flash independent-judge rescore of the same 40 baseline packages preserves the system-level ranking, with FirstResearch scoring 4.86/5 versus 4.38/5 for the strongest baseline and Pearson agreement of 0.865 on average score. A one-repeat ablation checkpoint further suggests that the certificate-centered core is the strongest component: certificate-only scoring reaches 4.90/5 under DeepSeek and 4.88/5 under Gemini, while removing certificates drops below 1/5 under both judges. These results are preliminary and use LLM judges rather than human domain experts, but they support a narrow scientific-discovery claim: explicit derivation constraints are a promising mechanism for making LLM-generated scientific questions more auditable. Code, prompts, saved outputs, and reproduction scripts are available at https://github.com/louiswang524/FirstResearch.