Preprint—not peer reviewed
Structure-free, site-resolved contrastive learning extends small-molecule discovery beyond the reach of structure-based modeling
Ptarmigan-1 contrastively co-embeds protein residues and candidate small molecules from sequence and two-dimensional chemistry, avoiding explicit pose construction. The authors report that it matches or exceeds docking and co-folding models at covalent, cryptic, and disordered sites, and screens 3.4 billion compounds across the human proteome in under a day. A residue-resolved, pose-free index could extend virtual screening to targets where structural pockets are unavailable or poorly defined.
AI–biochemistryAI–chemistry Molecular representation