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Bibliographic Details
Main Authors: Guo, Jeff, Schwaller, Philippe
Format: Preprint
Published: 2024
Subjects:
Online Access:https://arxiv.org/abs/2407.12186
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Table of 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.