ARTFEED — Contemporary Art Intelligence

ProtLiD²: Ligand-Conditioned Discrete Diffusion for Protein Design

publication · 2026-05-28

ProtLiD² represents an innovative discrete diffusion model aimed at co-designing protein sequences and structures with specific ligand constraints. This model simultaneously creates amino acid sequences and discrete structural tokens, utilizing geometry-aware cross-attention to integrate both chemical and geometric details of ligands. With training on more than one million ligand-protein complexes, ProtLiD² enhances masked discrete diffusion, facilitating ligand-aware protein design and filling a void in current discrete diffusion protein language models that lack direct conditioning from small molecules. The introduction of this model can be found in a preprint on arXiv (2605.27413).

Key facts

  • ProtLiD² is a ligand-conditioned discrete diffusion model for protein sequence-structure co-design.
  • It jointly generates amino-acid sequence and discrete structure tokens.
  • It incorporates ligand chemical and geometric information through geometry-aware cross-attention.
  • Trained on over one million ligand-protein complexes.
  • Extends masked discrete diffusion for ligand-aware protein design.
  • Addresses limitations of existing discrete diffusion protein language models.
  • Published as arXiv preprint 2605.27413.
  • The model enables design of sequence-structure compatible proteins under explicit ligand constraints.

Entities

Institutions

  • arXiv

Sources