Beyond Scaffold Splits: Structural-Frontier Evaluation Reveals Hidden Failures in ADMET Models

Excerpt

arXiv:2607.10729v4 Announce Type: replace Abstract: Molecular property models are commonly evaluated by holding out Bemis-Murcko scaffolds, yet a scaffold identifier is only one notion of chemical unfamiliarity. We introduce a label-free structural-frontier split that reserves the sparsest and most physicochemically remote scaffold groups, and evaluate it on six public experimental or curated ADMET tasks. Against a 70/10/20 scaffold control with identical acyclic grouping, the frontier inflates