QBioFusion-QSAR: Morgan-Anchored Quantum Multiple Kernel Learning for Small-Data Ligand Classification

Quantitative Structure-Activity Relationship ($\mathtt{QSAR}$) modeling is a foundational computational methodology in early-stage drug discovery, heavily relied upon for predicting compound toxicity, bioavailability, and therapeutic potential. However, classical methods often struggle to effectively map the highly complex, non-linear, and high-dimensional interactions inherent in molecular data, leading to reduced predictive accuracy and costly late-stage clinical failures. In this paper, we present a Quantum Multiple Kernel Learning ($\mathtt{QMKL}$) framework, dubbed Next-Gen $\mathtt{Q^2SAR}$, that leverages Quantum Support Vector Machines ($\mathtt{QSVMs}$) to overcome these classical limitations. By encoding molecular descriptors into exponentially large quantum Hilbert spaces, our approach substantially enhances the expressiveness of non-linear modeling. Benchmarking our quantum-enhanced framework on a dataset targeting the $\mathtt{DYRK1A}$ kinase (a critical target for Alzheimer's disease), the $\mathtt{QMKL}$-$\mathtt{SVM}$ achieves an impressive Area Under the Curve ($\mathtt{AUC}$) score of $0.8750$, significantly outperforming classical state-of-the-art Gradient Boosting models ($\mathtt{AUC} = 0.8037$). Furthermore, we establish a theoretical and empirical pathway toward resolving classical data bottlenecks through projected quantum kernels ($\mathtt{PQK}$) and measurement accelerators. As quantum computing architecture matures, this framework paves the way for autonomous cognitive architectures and self-improving drug discovery pipelines, promising to unlock deeper insights across vast chemical spaces and to accelerate the development of life-saving therapeutics.

Quantum kernel methods have been proposed as a promising approach for leveraging near-term quantum computers for supervised learning, yet rigorous benchmarks against strong classical baselines remain scarce. We present a comprehensive empirical study of quantum kernel support vector machines (QSVMs) across nine binary classification datasets, four quantum feature maps, three classical kernels, and multiple noise models, totalling 970 experiments with strict nested cross-validation. Our analysis spans four phases: (i) statistical significance testing, revealing that none of 29 pairwise quantum-classical comparisons reach significance at $α= 0.05$; (ii) learning curve analysis over six training fractions, showing steeper quantum slopes on six of eight datasets that nonetheless fail to close the gap to the best classical baseline; (iii) hardware validation on IBM ibm_fez (Heron r2), demonstrating kernel fidelity $r \geq 0.976$ across six experiments; and (iv) seed sensitivity analysis confirming reproducibility (mean CV 1.4%). A Kruskal-Wallis factorial analysis reveals that dataset choice dominates performance variance ($\varepsilon^2 = 0.73$), while kernel type accounts for only 9%. Spectral analysis offers a mechanistic explanation: current quantum feature maps produce eigenspectra that are either too flat or too concentrated, missing the intermediate profile of the best classical kernel, the radial basis function (RBF). Quantum kernel training (QKT) via kernel-target alignment yields the single competitive result -- balanced accuracy 0.968 on breast cancer -- but with ~2,000x computational overhead. Our findings provide actionable guidelines for quantum kernel research. The complete benchmark suite is publicly available to facilitate reproduction and extension.

We provide evidence of quantum kernel advantage under noiseless simulation in binary insurance classification on MIMIC-CXR chest radiographs using quantum support vector machines (QSVM) with frozen embeddings from three medical foundation models (MedSigLIP-448, RAD-DINO, ViT-patch32). We propose a two-tier fair comparison framework in which both classifiers receive identical PCA-q features. At Tier 1 (untuned QSVM vs. untuned linear SVM, C = 1 both sides), QSVM wins minority-class F1 in all 18 tested configurations (17 at p < 0.001, 1 at p < 0.01). The classical linear kernel collapses to majority-class prediction on 90-100% of seeds at every qubit count, while QSVM maintains non-trivial recall. At q = 11 (MedSigLIP-448 plateau center), QSVM achieves mean F1 = 0.343 vs. classical F1 = 0.050 (F1 gain = +0.293, p < 0.001) without hyperparameter tuning. Under Tier 2 (untuned QSVM vs. C-tuned RBF SVM), QSVM wins all seven tested configurations (mean gain +0.068, max +0.112). Eigenspectrum analysis reveals quantum kernel effective rank reaches 69.80 at q = 11, far exceeding linear kernel rank, while classical collapse remains C-invariant. A full qubit sweep reveals architecture-dependent concentration onset across models. Code: https://github.com/sebasmos/qml-medimage