将预训练全原子表示泛化到统一结合剂设计

arXiv:2610.37994v1 Announce Type: cross Abstract: PairFormer-based all-atom models demonstrate strong capabilities in biomolecular binder design. However, existing methods often use all-atom representations for modality-specific binder design, such as protein and peptide design. In contrast, recent geometric latent diffusion models pursue unified binder design by representing molecular blocks from different modalities in a shared latent space. These complementary strengths motivate us to investigate how to generalize the use of pretrained all-atom representations to unified binder design. We introduce PairFuse, a parameter-efficient method that enables this generalization through representation fusion. Specifically, we use lightweight layerwise adapters to integrate pretrained all-atom representations into an independently pretrained geometric latent diffusion model. Our adapters integrate pretrained all-atom representations through two mechanisms: enriching the diffusion model's molecular block features and incorporating pairwise structural information into the geometric diffusion model's denoiser. Theoretically, we prove that the augmented denoiser preserves geometry and pairwise attention fusion provides additional attention expressivity beyond feature-only fusion. Experimentally, across antibody, peptide, and small molecule binder-design benchmarks, PairFuse achieves stronger performance than the pretrained diffusion model and existing representation-fusion baselines.