Complete Donor-Set Guidance for Frozen Diffusion Docking Models

Hyunwoo Kim, Insoo Park, Ziseok Lee, Wooyeol Lee, Yoorim Gang +1

Metalloprotein docking requires a ligand pose to satisfy both global pocket fit and the identity and geometry of metal-coordinating atoms. General-purpose diffusion docking models do not explicitly condition generation on externally specified complete ligand donor sets, and their predicted poses can exhibit incorrect metal-donor relationships. Metal-aware models address coordination during training and generation; here we ask whether external donor information can correct already-trained general-purpose models without retraining. We propose Complete-Identity Contract Guidance (CICG), which applies a supplied complete donor set through translation, rotation, and torsion updates, and Historical Contract Transfer (HCT), which supplies donor identities from earlier complexes at compatible receptor sites. We compare HCT with trajectory-local controls retaining the historical donor count with or without elemental composition. On 86 assessable HCT-covered queries, HCT-guided CICG increases frozen-confidence-selected joint success from 21.5% to 36.6% on SurfDock and from 25.0% to 34.9% on DiffDock-L. The joint criterion requires correct global ligand placement, complete native donor…