Synthesis planning aiming to find pathways of reactions for a target molecule is one of the most important and challenging tasks in drug discovery. Recent progress has produced both specialized deep-learning retrosynthesis systems and general-purpose large language models, but objective comparison remains difficult due to the lack of flexible, chemically interpretable benchmarking protocols. In the current study, we are introducing the URSA (Utilitarian RetroSynthesis Assessment) evaluation framework that provides the opportunity to benchmark the synthetic routes not only from a formal perspective, such as convergence to commercially available starting materials, but also from a chemical plausibility perspective, mimicking the way expert chemists evaluate the reactions and routes. The study covers a comprehensive evaluation of both conventional end-to-end retrosynthesis solutions and LLMs for the synthesis planning task on a set of novel, diverse target molecules with undisclosed synthetic routes, which represent realistic tasks in the daily drug design routine. We find that while LLMs can support high-level strategic planning, they currently underperform specialized retrosynthesis models in reliably solving synthesis planning tasks.
B. Zagribelnyy, Ivan D. Ilin, N. Bondarev et al.· 0 citations
Large language models (LLMs) remain expensive to fine-tune because full-parameter updates require substantial memory, compute, and per-task storage. We study whether saliency signals originally developed for pruning can be reused to choose where a model should adapt. We propose Super, a sparse parameter-efficient fine-tuning (PEFT) method that fixes a small trainable support using a Wanda-style activation-weighted magnitude score [Sun et al., 2023] computed from a calibration pass. We then introduce Supra, a hybrid adapter that combines this sparse update with LoRA while preserving a matched trainable-parameter budget through a simple budget-splitting rule. In single-seed Math17K arithmetic experiments on Llama-3.2-1B and Meta-Llama-3-8B, the best Super/Supra variants achieve the highest average accuracy among the tested schedule-selected adapter configurations. We also include a PaFi-style magnitude-only support as a closest training-free sparse baseline and find that low-score supports under both magnitude and Wanda-style orderings can be effective. These results suggest that simple pruning-inspired orderings can provide useful fixed sparse supports for PEFT, especially when combined with low-rank adapters.
Ivan D. Ilin, Philip Zmushko, Peter Richtárik· 0 citations
This work introduces Top-K prompting as a robust training and inference paradigm to better capture diverse, plausible reaction predictions and establishes Top-K, plausibility-aware training as a practical new direction for robust future LLM-based synthesis planning.
B. Zagribelnyy, Ivan D. Ilin, N. Bondarev et al.· 0 citations