arXiv subjects

Lorenzo Di Fruscia

Publications and source records attributed to Lorenzo Di Fruscia.

3 recordsLinked to original sources

arXiv2026

Structural Hierarchy and Geometry in Molecular Representation Learning

Molecular self-supervised learning uses chemical structures to guide which molecular embeddings should be similar. We study whether explicitly encoding a molecule's Bemis-Murcko scaffold and using it to supervise the molecular embedding changes what the model learns. We further test whether this effect depends on the embedding geometry by comparing Euclidean and Lorentz contrastive objectives. Across two augmentation strengths, scaffold-supervised models consistently organize molecules according to both identical and structurally related scaffolds. The resulting embeddings also improve molecular property prediction on several tasks, while the exact gains depend on the predicted property. The effect of scaffold supervision on molecular organization is stronger under Lorentz objectives, but neither geometry provides a consistent overall advantage. These results show that explicitly teaching the relation between a molecule and its structural core can reliably shape the organization of molecular embedding space, while the extent of usefulness of this organization remains task dependent.

cs.LG↗

arXiv2026

Grounding Large Language Models in Reaction Knowledge Graphs for Synthesis Retrieval

Large Language Models (LLMs) can aid synthesis planning in chemistry, but standard prompting methods often yield hallucinated or outdated suggestions. We study LLM interactions with a reaction knowledge graph by casting reaction path retrieval as a Text2Cypher (natural language to graph query) generation problem, and define single- and multi-step retrieval tasks. We compare zero-shot prompting to one-shot variants using static, random, and embedding-based exemplar selection, and assess a checklist-driven validator/corrector loop. To evaluate our framework, we consider query validity and retrieval accuracy. We find that one-shot prompting with aligned exemplars consistently performs best. Our checklist-style self-correction loop mainly improves executability in zero-shot settings and offers limited additional retrieval gains once a good exemplar is present. We provide a reproducible Text2Cypher evaluation setup to facilitate further work on KG-grounded LLMs for synthesis planning. Code is available at https://github.com/Intelligent-molecular-systems/KG-LLM-Synthesis-Retrieval.

cs.AI↗

arXiv2025

Leveraging Large Language Models for enzymatic reaction prediction and characterization

Predicting enzymatic reactions is crucial for applications in biocatalysis, metabolic engineering, and drug discovery, yet it remains a complex and resource-intensive task. Large Language Models (LLMs) have recently demonstrated remarkable success in various scientific domains, e.g., through their ability to generalize knowledge, reason over complex structures, and leverage in-context learning strategies. In this study, we systematically evaluate the capability of LLMs, particularly the Llama-3.1 family (8B and 70B), across three core biochemical tasks: Enzyme Commission number prediction, forward synthesis, and retrosynthesis. We compare single-task and multitask learning strategies, employing parameter-efficient fine-tuning via LoRA adapters. Additionally, we assess performance across different data regimes to explore their adaptability in low-data settings. Our results demonstrate that fine-tuned LLMs capture biochemical knowledge, with multitask learning enhancing forward- and retrosynthesis predictions by leveraging shared enzymatic information. We also identify key limitations, for example challenges in hierarchical EC classification schemes, highlighting areas for further improvement in LLM-driven biochemical modeling.

cs.AI↗