What happened
Peptides occupy a valuable niche between small molecules and biologics, but the clinical translation of de novo peptide designs requires rigorous scoring to simultaneously optimise target binding affinity alongside multiple developability traits, including stability, membrane permeability, aggregation propensity, and non-fouling behaviour. Here, we evaluate two distinct approaches for scoring these candidates: classical chemical descriptors and modern deep learning representations derived from protein language and folding models. Assembling nine public datasets spanning five developability traits and four binding-affinity endpoints, we find sequence-derived chemical descriptors alone contain sufficient information to predict developability task labels effectively. Given their drastically lower computational cost and higher interpretability, classical machine learning models trained on these simple descriptors frequently match or approach the performance of complex deep learning architectures, emerging as a highly efficient and interpretable alternative for high-throughput scoring. Finally, for scoring binding affinity, we demonstrate that Boltz-2 pair representations capture the most information among the tested representations; however, the model's predictive power is confounded by a significant bias from the molecular weight of the peptides. Together, these results establish a comprehensive assessment of state-of-the-art methods for predicting both peptide developability and binding affinity, highlighting the enduring value of interpretable chemical descriptors alongside deep learning in the scoring and selection of de novo peptide designs.