PepSAGE: Hierarchical All-Atom Peptide Generation with Continuous Local-Geometry States

Peptides can engage protein surfaces that are difficult to target with small molecules, making pocket-conditioned peptide design a valuable yet challenging therapeutic goal. Generating such peptides at all-atom resolution requires the joint modeling of global backbone pose, amino-acid identity, and residue-internal atomic conformation. Existing representations face a persistent tension between expressive local detail and geometric validity: Cartesian coordinates expose rigid-body redundancy, torsion variables are chemically grounded but less convenient as a uniform learned interface across residue types, and discrete structural tokens may discard fine conformational variation. We introduce a geometry-state generation formulation for pocket-conditioned all-atom peptide design, instantiated as PepSAGE (Peptide Structure-Aware Generation). Rather than directly generating unconstrained atom coordinates, relying on residue-specific torsions, or discretizing local structure into tokens, PepSAGE represents residue-internal conformation with a shared six-dimensional continuous state ($z\in {\mathbb{R}}^6$), while modeling residue pose and amino-acid identity through separate channels. This state is learned through a reconstruction interface that is frozen during generation, allowing PepSAGE to generate continuous pre-quantization local geometry and recover all-atom structures through a geometry-constrained reconstruction pathway. Under a unified training budget and leakage-controlled evaluation, PepSAGE achieves the best backbone, all-atom, and side-chain RMSD, the lowest clash, and the highest rotamer recovery among competitive baselines, with additional analyses showing a tunable quality–diversity trade-off. Controlled ablations show that the continuous local-geometry channel drives side-chain recovery, while geometry-constrained reconstruction improves geometric validity, supporting continuous local geometry as an effective internal state for structured all-atom peptide generation.