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Main Authors: Guo, Jeff, Schwaller, Philippe
Format: Preprint
Published: 2024
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Online Access:https://arxiv.org/abs/2407.12186
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author Guo, Jeff
Schwaller, Philippe
author_facet Guo, Jeff
Schwaller, Philippe
contents Synthesizability in generative molecular design remains a pressing challenge. Existing methods to assess synthesizability span heuristics-based methods, retrosynthesis models, and synthesizability-constrained molecular generation. The latter has become increasingly prevalent and proceeds by defining a set of permitted actions a model can take when generating molecules, such that all generations are anchored in "synthetically-feasible" chemical transformations. To date, retrosynthesis models have been mostly used as a post-hoc filtering tool as their inference cost remains prohibitive to use directly in an optimization loop. In this work, we show that with a sufficiently sample-efficient generative model, it is straightforward to directly optimize for synthesizability using retrosynthesis models in goal-directed generation. Under a heavily-constrained computational budget, our model can generate molecules satisfying a multi-parameter drug discovery optimization task while being synthesizable, as deemed by the retrosynthesis model.
format Preprint
id arxiv_https___arxiv_org_abs_2407_12186
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Directly Optimizing for Synthesizability in Generative Molecular Design using Retrosynthesis Models
Guo, Jeff
Schwaller, Philippe
Biomolecules
Synthesizability in generative molecular design remains a pressing challenge. Existing methods to assess synthesizability span heuristics-based methods, retrosynthesis models, and synthesizability-constrained molecular generation. The latter has become increasingly prevalent and proceeds by defining a set of permitted actions a model can take when generating molecules, such that all generations are anchored in "synthetically-feasible" chemical transformations. To date, retrosynthesis models have been mostly used as a post-hoc filtering tool as their inference cost remains prohibitive to use directly in an optimization loop. In this work, we show that with a sufficiently sample-efficient generative model, it is straightforward to directly optimize for synthesizability using retrosynthesis models in goal-directed generation. Under a heavily-constrained computational budget, our model can generate molecules satisfying a multi-parameter drug discovery optimization task while being synthesizable, as deemed by the retrosynthesis model.
title Directly Optimizing for Synthesizability in Generative Molecular Design using Retrosynthesis Models
topic Biomolecules
url https://arxiv.org/abs/2407.12186