WEECFP-SuRGE: A Position-Aware Substructure Encoding Method for Molecular Property Prediction

Özetle: Computational molecular property prediction requires representations that capture local chemistry, long-range interactions, and molecular topology.

Özet

Computational molecular property prediction requires representations that capture local chemistry, long-range interactions, and molecular topology. Conventional fingerprints provide efficient local substructure features, whereas learned graph and sequence models can represent broader context but often rely on pretraining or three-dimensional conformers. We introduce Wide Encoded Extended Connectivity Fingerprints (WEECFP) with Substructure Rotary Graph-distance Encoding (SuRGE), a tokenized hierarchical Morgan representation in which graph-distance-dependent rotations are applied at the input and within transformer self-attention. Across MoleculeNet and the Therapeutic Data Commons ADMET benchmarks, WEECFP-SuRGE is competitive with recent pretrained and geometry-aware methods without external pretraining or conformer generation. We also show that the rotated token representation remains structurally informative. A guided confirmed-handshake overlap procedure reconstructs the correct constitutional isomer for 92.6% of a 4,200-molecule self-library evaluation. Together, the predictive and reconstruction results indicate that WEECFP-SuRGE preserves local substructure identity while making relative topology available to the model.

Orijinal Özet (İngilizce)

Computational molecular property prediction requires representations that capture local chemistry, long-range interactions, and molecular topology. Conventional fingerprints provide efficient local substructure features, whereas learned graph and sequence models can represent broader context but often rely on pretraining or three-dimensional conformers. We introduce Wide Encoded Extended Connectivity Fingerprints (WEECFP) with Substructure Rotary Graph-distance Encoding (SuRGE), a tokenized hierarchical Morgan representation in which graph-distance-dependent rotations are applied at the input and within transformer self-attention. Across MoleculeNet and the Therapeutic Data Commons ADMET benchmarks, WEECFP-SuRGE is competitive with recent pretrained and geometry-aware methods without external pretraining or conformer generation. We also show that the rotated token representation remains structurally informative. A guided confirmed-handshake overlap procedure reconstructs the correct constitutional isomer for 92.6% of a 4,200-molecule self-library evaluation. Together, the predictive and reconstruction results indicate that WEECFP-SuRGE preserves local substructure identity while making relative topology available to the model.

Kaynak: arXiv:2609.04672 · PDF