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cs.AI updates on arXiv.org

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
ReACT-Drug: Reaction-Template Guided Reinforcement Learni...
R Yadunandan, Nimisha Ghosh · 2025-12-24 · via cs.AI updates on arXiv.org

De novo drug design is a crucial component of modern drug development, yet navigating the vast chemical space to find synthetically accessible, high-affinity candidates remains a significant challenge. Reinforcement Learning (RL) enhances this process by enabling multi-objective optimization and exploration of novel chemical space - capabilities that traditional supervised learning methods lack. In this work, we introduce \textbf{ReACT-Drug}, a fully integrated, target-agnostic molecular design framework based on Reinforcement Learning. Unlike models requiring target-specific fine-tuning, ReACT-Drug utilizes a generalist approach by leveraging ESM-2 protein embeddings to identify similar proteins for a given target from a knowledge base such as Protein Data Base (PDB). Thereafter, the known drug ligands corresponding to such proteins are decomposed to initialize a fragment-based search space, biasing the agent towards biologically relevant subspaces. For each such fragment, the pipeline employs a Proximal Policy Optimization (PPO) agent guiding a ChemBERTa-encoded molecule through a dynamic action space of chemically valid, reaction-template-based transformations. This results in the generation of \textit{de novo} drug candidates with competitive binding affinities and high synthetic accessibility, while ensuring 100\% chemical validity and novelty as per MOSES benchmarking. This architecture highlights the potential of integrating structural biology, deep representation learning, and chemical synthesis rules to automate and accelerate rational drug design. The dataset and code are available at https://github.com/YadunandanRaman/ReACT-Drug/.