Transformer-based, template-free SMILES-to-SMILES translation models for reaction prediction and single-step retrosynthesis are of interest to computer-aided synthesis planning systems, as they offer state-of-the-art accuracy. However, their slow inference speed limits their practical utility in such applications. To address this challenge, we propose speculative decoding with a simple chemically specific drafting strategy and apply it to the Molecular Transformer, an encoder-decoder transformer for conditional SMILES generation. Our approach achieves over 3X faster inference in reaction product prediction and single-step retrosynthesis with no loss in accuracy, increasing the potential of the transformer as the backbone of synthesis planning systems. To accelerate the simultaneous generation of multiple precursor SMILES for a given query SMILES in single-step retrosynthesis, we introduce Speculative Beam Search, a novel algorithm tackling the challenge of beam search acceleration with speculative decoding. Our methods aim to improve transformer-based models' scalability and industrial applicability in synthesis planning.

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13321-025-00974-wDOI Listing

Publication Analysis

Top Keywords

single-step retrosynthesis
12
synthesis planning
12
prediction single-step
8
planning systems
8
speculative decoding
8
beam search
8
accelerating inference
4
inference string
4
string generation-based
4
generation-based chemical
4

Similar Publications

Transformer-based, template-free SMILES-to-SMILES translation models for reaction prediction and single-step retrosynthesis are of interest to computer-aided synthesis planning systems, as they offer state-of-the-art accuracy. However, their slow inference speed limits their practical utility in such applications. To address this challenge, we propose speculative decoding with a simple chemically specific drafting strategy and apply it to the Molecular Transformer, an encoder-decoder transformer for conditional SMILES generation.

View Article and Find Full Text PDF

Improving route development using convergent retrosynthesis planning.

J Cheminform

February 2025

In-Silico Discovery, Research & Development, Johnson & Johnson, Cambridge, 02142, US.

Retrosynthesis consists of recursively breaking down a target molecule to produce a synthesis route composed of readily accessible building blocks. In recent years, computer-aided synthesis planning methods have allowed a greater exploration of potential synthesis routes, combining state-of-the-art machine-learning methods with chemical knowledge. However, these methods are generally developed to produce individual routes from a singular product to a set of proposed building blocks and are not designed to leverage potential shared paths between targets.

View Article and Find Full Text PDF

Investigations into the Efficiency of Computer-Aided Synthesis Planning.

J Chem Inf Model

February 2025

Molecular AI, Discovery Sciences, R&D, AstraZeneca, Pepparedsleden 1, 431 83 Mölndal, Sweden.

The efficiency of machine learning (ML) models is crucial to minimize inference times and reduce the carbon footprints of models deployed in production environments. Current models employed in retrosynthesis to generate a synthesis route from a target molecule to purchasable compounds are prohibitively slow. The model operates in a single-step fashion in a tree search algorithm by predicting reactant molecules given a product molecule as input.

View Article and Find Full Text PDF

Retrosynthesis is a strategy to analyze the synthetic routes for target molecules in medicinal chemistry. However, traditional retrosynthesis predictions performed by chemists and rule-based expert systems struggle to adapt to the vast chemical space of real-world scenarios. Artificial intelligence (AI) has revolutionized retrosynthesis prediction in recent decades, significantly increasing the accuracy and diversity of predictions for target compounds.

View Article and Find Full Text PDF

Inferring appropriate synthesis reaction (i.e., retrosynthesis) routes for newly designed molecules is vital.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!