• Propose PPIFlow, a flow-matching model that achieves picomolar to nanomolar affinities across diverse targets, including 7/8 high-affinity VHHs, fully in silico
• Combine Pairformer and Invariant Point Attention modules, trained through a four-stage curriculum: monomer and motif scaffolding, binder design, scFv design, VHH design
• Develop an in silico maturation pipeline: (i) Identify interface residues with interaction energy < −5 REU across designed sequences (ii) Merge into a consensus set of anchor rotamers (iii) Fix anchors, apply noise (t = 0.6), and perform partial flow refinement to regenerate unconstrained backbone (iv) Redesign sequences Final candidates are filtered with pTM > 0.8 and ipTM > 0.5 with AF3score