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Policy Split: Incentivizing Dual-Mode Exploration in LLM Reinforcement with Dual-Mode Entropy Regularization METER: Evaluating Multi-Level Contextual Causal Reasoning in Large Language Models Think Before you Write: QA-Guided Reasoning for Character Descriptions in Books METRO: Towards Strategy Induction from Expert Dialogue Transcripts for Non-collaborative Dialogues Retrieval as Generation: A Unified Framework with Self-Triggered Information Planning Do LLMs Know Tool Irrelevance? Demystifying Structural Alignment Bias in Tool Invocations Enhancing Multimodal Large Language Models for Ancient Chinese Character Evolution Analysis via Glyph-Driven Fine-Tuning Exploring Knowledge Conflicts for Faithful LLM Reasoning: Benchmark and Method CocoaBench: Evaluating Unified Digital Agents in the Wild MathAgent: Adversarial Evolution of Constraint Graphs for Mathematical Reasoning Data Synthesis Efficient Training for Cross-lingual Speech Language Models Shared Emotion Geometry Across Small Language Models: A Cross-Architecture Study of Representation, Behavior, and Methodological Confounds A Systematic Analysis of the Impact of Persona Steering on LLM Capabilities Uncertainty-Aware Web-Conditioned Scientific Fact-Checking When Valid Signals Fail: Regime Boundaries Between LLM Features and RL Trading Policies When Verification Fails: How Compositionally Infeasible Claims Escape Rejection Mem$^2$Evolve: Towards Self-Evolving Agents via Co-Evolutionary Capability Expansion and Experience Distillation AOP-Smart: A RAG-Enhanced Large Language Model Framework for Adverse Outcome Pathway Analysis Advancing Polish Language Modeling through Tokenizer Optimization in the Bielik v3 7B and 11B Series TInR: Exploring Tool-Internalized Reasoning in Large Language Models Do BERT Embeddings Encode Narrative Dimensions? A Token-Level Probing Analysis of Time, Space, Causality, and Character in Fiction Generating Multiple-Choice Knowledge Questions with Interpretable Difficulty Estimation using Knowledge Graphs and Large Language Models Deep-Reporter: Deep Research for Grounded Multimodal Long-Form Generation Too Nice to Tell the Truth: Quantifying Agreeableness-Driven Sycophancy in Role-Playing Language Models Learning and Enforcing Context-Sensitive Control for LLMs Efficient Process Reward Modeling via Contrastive Mutual Information Computational Lesions in Multilingual Language Models Separate Shared and Language-specific Brain Alignment Bridging Linguistic Gaps: Cross-Lingual Mapping in Pre-Training and Dataset for Enhanced Multilingual LLM Performance Early Decisions Matter: Proximity Bias and Initial Trajectory Shaping in Non-Autoregressive Diffusion Language Models LLMs Should Incorporate Explicit Mechanisms for Human Empathy
Reinforcement Learning with LLM-Guided Action Spaces for ...
Tao Li, Kaiyuan Hou, Tuan Vinh, Monika Raj, Zhichun Guo, Carl Ya · 2026-04-09 · via cs.AI updates on arXiv.org

Lead optimization in drug discovery requires improving therapeutic properties while ensuring that molecular modifications correspond to feasible synthetic routes. Existing approaches either prioritize property scores without enforcing synthesizability, or rely on expensive enumeration over large reaction networks, while direct application of Large Language Models (LLMs) to molecular generation frequently produces chemically invalid structures. We introduce MolReAct, a framework that formulates lead optimization as a Markov Decision Process over a synthesis-constrained action space defined by validated reaction templates. A tool-augmented LLM agent serves as a dynamic reaction environment, invoking specialized chemical analysis tools to identify reactive sites and functional groups and proposing a compact set of chemically grounded transformations from matched templates. A dedicated policy model trained via Group Relative Policy Optimization (GRPO) selects among these constrained actions to maximize long-term oracle reward across multi-step trajectories, with a SMILES-based caching mechanism reducing end-to-end optimization time by approximately 43%. Across 13 property optimization tasks from the Therapeutic Data Commons and one structure-based docking task, MolReAct achieves an average Top-10 score of 0.571, the highest among all baselines, ranking first or second on 13 of 14 tasks and attaining the best sample efficiency on 9 of 14 tasks. By grounding every optimization step in validated reaction templates, MolReAct produces molecules that are not only property-improved but each accompanied by an explicit template-grounded synthetic pathway.