A Structure-Informed Atlas of Venom-Derived Peptides Reveals the Organization of Chemical Space.

Venom-derived peptides are structurally diverse bioactive scaffolds with growing relevance for computational discovery and molecular design. However, their organization within chemical space remains poorly characterized in integrated frameworks. Here, we present a curated, structure-informed venom peptide atlas supported by an integrated descriptor-based framework combining sequence- and structure-derived features across 3,423 peptides. High-confidence AlphaFold models were integrated with physicochemical and structural descriptors to generate a unified molecular representation. Multivariate analyses reveal that venom peptides occupy constrained and interpretable regions of chemical space shaped by disulfide-mediated stabilization, structural compactness, and electrostatic-hydrophobic balance. Functional classes show clear separation, whereas taxonomic origin explains less variance, supporting convergent design principles. This atlas provides a reference resource for comparative analyses, scaffold prioritization, and hypothesis generation in peptide science.