Quantum-Inspired Hamiltonian Feature Extraction for ADMET Prediction: A Simulation Study

Fuente: arXiv
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Auteurs principaux: Benson, B. Maurice, Byler, Kendall, Petroff, Anna, Keinan, Shahar, Shipman, William J
Format: Preprint
Publié: 2026
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author Benson, B. Maurice
Byler, Kendall
Petroff, Anna
Keinan, Shahar
Shipman, William J
author_facet Benson, B. Maurice
Byler, Kendall
Petroff, Anna
Keinan, Shahar
Shipman, William J
contents Predicting absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties remains a critical bottleneck in drug discovery. While molecular fingerprints effectively capture local structural features, they struggle to represent higher-order correlations among molecular substructures. We present a quantum-inspired feature extraction method that encodes molecular fingerprints into a parameterized Hamiltonian, using mutual information (MI) to guide entanglement structure. By simulating quantum evolution on GPU-accelerated backends, we extract expectation values that capture pairwise and triadic correlations among fingerprint bits. On ten Therapeutic Data Commons (TDC) ADMET benchmarks, our method achieves state-of-the-art performance on CYP3A4 substrate prediction (AUROC 0.673 0.004) and improves over classical baselines on 8/10 tasks. SHAP (SHapley Additive exPlanations) analysis reveals that quantum-derived features contribute up to 33% of model importance despite comprising only 1.6% of features, demonstrating that Hamiltonian encoding concentrates predictive signal. This simulation study establishes the foundation for hardware validation on near-term quantum devices.
format Preprint
id arxiv_https___arxiv_org_abs_2603_03109
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Quantum-Inspired Hamiltonian Feature Extraction for ADMET Prediction: A Simulation Study
Benson, B. Maurice
Byler, Kendall
Petroff, Anna
Keinan, Shahar
Shipman, William J
Quantum Physics
Predicting absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties remains a critical bottleneck in drug discovery. While molecular fingerprints effectively capture local structural features, they struggle to represent higher-order correlations among molecular substructures. We present a quantum-inspired feature extraction method that encodes molecular fingerprints into a parameterized Hamiltonian, using mutual information (MI) to guide entanglement structure. By simulating quantum evolution on GPU-accelerated backends, we extract expectation values that capture pairwise and triadic correlations among fingerprint bits. On ten Therapeutic Data Commons (TDC) ADMET benchmarks, our method achieves state-of-the-art performance on CYP3A4 substrate prediction (AUROC 0.673 0.004) and improves over classical baselines on 8/10 tasks. SHAP (SHapley Additive exPlanations) analysis reveals that quantum-derived features contribute up to 33% of model importance despite comprising only 1.6% of features, demonstrating that Hamiltonian encoding concentrates predictive signal. This simulation study establishes the foundation for hardware validation on near-term quantum devices.
title Quantum-Inspired Hamiltonian Feature Extraction for ADMET Prediction: A Simulation Study
topic Quantum Physics
url https://arxiv.org/abs/2603.03109