arXiv:2603.11061physics.chem-phcs.AI2026-03被引 1

用量子启发特征增强蛋白残基pKa预测,提升跨环境泛化能力。

Hybrid Quantum-Classical Encoding for Accurate Residue-Level pKa Prediction

  • 融合量子核映射与结构特征,构建混合编码表示
  • 在多个数据集上实现比经典模型更强的跨场景泛化
  • 适用于蛋白电荷特性研究,尤其适合复杂微环境建模

准确预测残基级pKa值对理解蛋白质功能、稳定性和反应性至关重要。现有资源如DeepKaDB和CpHMD衍生数据集虽提供宝贵训练数据,但其描述符仍以经典为主,常难以在多样化生化环境中泛化。本文提出可复现的量子-经典混合框架,通过基于高斯核的量子启发特征映射丰富残基表征。这些量子增强特征与归一化结构特征结合,形成统一混合编码,输入深度量子神经网络(DQNN)以捕捉经典模型无法获取的残基微环境非线性关系。在多个精选描述符集上的基准测试表明,DQNN相比经典基线展现出更优的跨上下文泛化能力。外部评估在PKAD-R实验基准及Aβ40案例研究中进一步验证了该量子启发表示的鲁棒性与可迁移性。通过整合量子启发特征变换与经典生化描述符,本工作建立了一种可扩展且实验可迁移的残基级pKa预测方法,适用于更广泛的蛋白质静电学应用。

原文摘要 · Abstract (English)

Accurate prediction of residue-level pKa values is essential for understanding protein function, stability, and reactivity. While existing resources such as DeepKaDB and CpHMD-derived datasets provide valuable training data, their descriptors remain primarily classical and often struggle to generalize across diverse biochemical environments. We introduce a reproducible hybrid quantum-classical framework that enriches residue-level representations with a Gaussian kernel-based quantum-inspired feature mapping. These quantum-enhanced descriptors are combined with normalized structural features to form a unified hybrid encoding processed by a Deep Quantum Neural Network (DQNN). This architecture captures nonlinear relationships in residue microenvironments that are not accessible to classical models. Benchmarking across multiple curated descriptor sets demonstrates that the DQNN achieves improved cross-context generalization relative to classical baselines. External evaluation on the PKAD-R experimental benchmark and an A$β$40 case study further highlights the robustness and transferability of the quantum-inspired representation. By integrating quantum-inspired feature transformations with classical biochemical descriptors, this work establishes a scalable and experimentally transferable approach for residue-level pKa prediction and broader applications in protein electrostatics.

pKa预测量子启发蛋白质电荷特征融合

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