WEECFP-SuRGE: Wide Embedded Extended Connectivity Fingerprint with Substructure Rotary Graph-distance Encoding

Abstract:We introduce WEECFP, a parameter-free 1024-dimensional continuous molecular fingerprint that scatters each Morgan substructure across roughly thirty-two signed positions of a single vector, and WEECFP-SuRGE, a transformer architecture whose self-attention applies SuRGE (Substructure Rotary Graph-distance Encoding) -- a RoPE-like rotation parameterized by molecular shortest-path graph distance -- to WEECFP substructure tokens. A 7-model blend of this architecture (the WEECFP-SuRGE Blend) achieves the lowest average regression rank on the TDC ADMET leaderboard; is #2 overall on the TDC ADMET leaderboard (behind only pretrained MapLight+GNN), and is #1 overall among methods that use no external pretraining; takes leaderboard #1 finishes on Pgp, Lipophilicity, CYP2D6 Substrate, Clearance Microsome, and LD50 (with the WEECFP-NoSuRGE Blend separately reaching #1 on HIA) across the full 22-benchmark suite -- without any external pretraining. On MoleculeNet, WEECFP-SuRGE beats every classical-fingerprint baseline on 3 of 4 regression tasks (ESOL, Lipophilicity, QM9). We further show that WEECFP tokenization is near-lossless: a greedy overlap reconstruction recovers the exact canonical SMILES of 99.9% of in-distribution molecules across 9 MoleculeNet datasets and 98.93% of molecules in a cross-dataset holdout (HIV->Lipophilicity), and that a three-reference farthest-first encoding of graph distance correlates at Pearson r = 0.901 with the true pairwise distance, enabling O(S) positional memory at matching accuracy.

Machine Learning (cs.LG)

arXiv:2609.04672 [cs.LG]

(or arXiv:2609.04672v1 [cs.LG] for this version)

https://doi.org/10.48550/arXiv.2609.04672 Focus to learn more arXiv-issued DOI via DataCite (pending registration)

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