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bioRxiv · 10.1101/2025.07.15.664910

Design in Voxel Space Decode in SMILES Space: Plixer Generates Drug-Like Molecules for Protein Pockets

Wells, J.·Paige, B.
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Abstract

We introduce Plixer, a two-stage generative model for de novo drug design that generates small-molecule ligand binders conditioned on an empty protein pocket. Plixer combines a conditional voxel inpainting network to generate 3D ligand hypotheses with an independently trained voxel-to-SMILES decoder that translates these voxel representations into valid chemical structures. By de-coupling the learning of spatial protein-ligand interactions from the learning of chemical grammar, our approach leverages large libraries of 3D ligand conformers to augment the limited data available for protein-ligand complexes. We show that this approach generates molecules with higher predicted binding affinity than recent methods.

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Wells, J., Paige, B.. 2025-07-18. Design in Voxel Space Decode in SMILES Space: Plixer Generates Drug-Like Molecules for Protein Pockets. https://doi.org/10.1101/2025.07.15.664910

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