RetroReasoner: A Reasoning LLM for Strategic Retrosynthesis Prediction

Retrosynthesis prediction is a core task in organic synthesis that aims to predict reactants for a given product molecule. Traditionally, chemists select a plausible bond disconnection and derive corresponding reactants, which is time-consuming and requires substantial expertise. While recent advancements in molecular large language models (LLMs) have made progress, many methods either predict reactants without strategic reasoning or conduct only a generic product analysis, rather than reason explicitly about bond-disconnection strategies that logically lead to the choice of specific reactants. To overcome these limitations, we propose RetroReasoner, a retrosynthetic reasoning model that leverages chemists' strategic thinking. RetroReasoner is trained using both supervised fine-tuning (SFT) and reinforcement learning (RL). For SFT, we introduce SyntheticRetro, a framework that generates structured disconnection rationales alongside reactant predictions. In the case of RL, we apply a round-trip accuracy as reward, where predicted reactants are passed through a forward synthesis model, and predictions are rewarded when the forward-predicted product matches the original input product. Experimental results show that RetroReasoner not only outperforms prior baselines but also generates a broader range of feasible reactant proposals, particularly in handling more challenging reaction instances.

Mol-LLM: Generalist Molecular LLM with Improved Graph Utilization

Recent advances in Large Language Models (LLMs) have motivated the development of general LLMs for molecular tasks. While several studies have demonstrated that fine-tuned LLMs can achieve impressive benchmark performances, they are far from genuine generalist molecular LLMs due to a lack of fundamental understanding of molecular structure. Specifically, when given molecular task instructions, LLMs trained with naive next-token prediction training assign similar likelihood scores to both original and negatively corrupted molecules, revealing their lack of molecular structure understanding that is crucial for reliable and general molecular LLMs. To overcome this limitation and obtain a true generalist molecular LLM, we introduce a novel multi-modal training method based on a thorough multi-modal instruction tuning as well as a molecular structure preference optimization between chosen and rejected graphs. On various molecular benchmarks, the proposed generalist molecular LLM, called Mol-LLM, achieves state-of-the-art performances among generalist LLMs on most tasks, at the same time, surpassing or comparable to state-of-the-art specialist LLMs. Moreover, Mol-LLM also shows superior generalization performances in reaction prediction tasks, demonstrating the effect of the molecular structure understanding for generalization perspective.

A Deep Reinforcement Learning Approach for Solving the Traveling Salesman Problem with Drone

Reinforcement learning has recently shown promise in learning quality solutions in many combinatorial optimization problems. In particular, the attention-based encoder-decoder models show high effectiveness on various routing problems, including the Traveling Salesman Problem (TSP). Unfortunately, they perform poorly for the TSP with Drone (TSP-D), requiring routing a heterogeneous fleet of vehicles in coordination -- a truck and a drone. In TSP-D, the two vehicles are moving in tandem and may need to wait at a node for the other vehicle to join. State-less attention-based decoder fails to make such coordination between vehicles. We propose an attention encoder-LSTM decoder hybrid model, in which the decoder's hidden state can represent the sequence of actions made. We empirically demonstrate that such a hybrid model improves upon a purely attention-based model for both solution quality and computational efficiency. Our experiments on the min-max Capacitated Vehicle Routing Problem (mmCVRP) also confirm that the hybrid model is more suitable for coordinated routing of multiple vehicles than the attention-based model.