GRASP: Graph Representation Learning with Assay Supervision for Molecular Properties

Abstract

Molecular structures are abundant, while experimental bioactivity is sparse and distributed across assays. We introduce GRASP, a 93.5M-parameter graph Transformer that learns from these sources in sequence. GRASP first learns molecular structure through replaced-token detection on 1.54 billion ZINC20 molecule presentations, then adapts to sparse bioactivity across 642 ChEMBL assays. Across 23 cluster-held-out OpenADMET endpoints, GRASP achieves a mean MAE of 0.374, compared with 0.383 for CheMeleon, 0.408 for ECFP4-LightGBM, and 0.440 for Chemprop. ChEMBL adaptation reduces mean MAE from 0.407 to 0.374 and improves 21 of 23 endpoints, showing the value of intermediate bioactivity supervision. On 22 TDC ADMET tasks, GRASP gives a better point estimate than CheMeleon on 13 tasks. These results support staged molecular representation learning, where abundant molecular structure and sparse experimental measurements provide complementary supervision at different stages of training.