Unified modeling of 3D molecular generation via atomic interactions with PocketXMol
Summary
We present PocketXMol, an atom-level model that unifies generative tasks related to protein pocket interactions. Using atomic prompts as task specifications, PocketXMol supports various molecular tasks, including structure prediction and de novo design of small molecules and peptides, without task-specific fine-tuning. PocketXMol achieved strong performance on 11 of 13 computational benchmarks and remained competitive on the remaining two, outperforming 55 baseline models. We applied Pocke
Content
# Unified modeling of 3D molecular generation via atomic interactions with PocketXMol
*Published: 2026 Apr 2*
We present PocketXMol, an atom-level model that unifies generative tasks related
to protein pocket interactions. Using atomic prompts as task specifications,
PocketXMol supports various molecular tasks, including structure prediction and
de novo design of small molecules and peptides, without task-specific
fine-tuning. PocketXMol achieved strong performance on 11 of 13 computational
benchmarks and remained competitive on the remaining two, outperforming 55
baseline models. We applied PocketXMol to design caspase-9-inhibiting small
molecules, achieving efficacy comparable with commercial pan-caspase inhibitors.
We also adopted PocketXMol to generate PD-L1-binding peptides, resulting in a
success rate that largely exceeds library screening. Three representative
peptides underwent further experiments, which validated their cellular
specificity and confirmed their potential for molecular probing and
therapeutics. PocketXMol provides a general platform for AI-aided drug discovery
and enables a wide range of future applications.
DOI: 10.1016/j.cell.2026.01.003