diff-hdx 0.1.0

Differentiable HDX-MS prediction in JAX

🧪 diff-hdx: Differentiable HDX-MS Prediction in JAX

diff-hdx is a high-performance Python library for differentiable Hydrogen-Deuterium Exchange (HDX-MS) prediction. Built on JAX, it provides auto-differentiable kernels to bridge structural ensembles and experimental protection factors.

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🎯 Features

• Differentiable SASA Kernels: Hardware-accelerated approximations of Solvent Accessible Surface Area using Gaussian occlusion models.
• Protection Factor Modeling: Implementations of Linderstrøm-Lang models for H-exchange rates ($PF$).
• Kinetic Simulation: Model time-dependent mass shifts using EX2 kinetics (Hvidt & Nielsen, 1966).
• Gradient-Based Refinement: Optimize protein structures or ensembles directly against experimental HDX-MS time-curves.
• Vectorized Execution: Native support for vmap to handle large conformational ensembles.

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🏗️ Technical Architecture

• Backend: JAX (XLA-compiled) — supports CPU, GPU, and TPU.
• Differentiability: Full support for forward and reverse-mode autodiff.
• Integration: Compatible with biotite for structural parsing and diff-biophys for ensemble averaging.

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🚀 Roadmap

• Initial differentiable SASA and $ln P$ kernels.
• Integration with JAX vmap for ensemble averaging.
• Residue-specific intrinsic exchange rates (Bai et al. 1993) — all 20 amino acids.
• Integration with MD trajectory loaders.

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🚀 Installation

pip install diff-hdx

🧪 Scientific Validation

• Parity Checks: Kernels are validated against standard non-differentiable implementations (e.g., biotite SASA) to ensure physical accuracy.
• Gradient Tests: All kernels are verified using JAX's gradcheck to ensure numerically stable derivatives across the full support.
• Ensemble Consistency: Verified against diff-biophys ensemble averaging for IDP conformational ensembles.

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🔗 Related Projects

diff-hdx is part of the differentiable biophysics ecosystem:

• diff-biophys — Core differentiable biophysics engine.
• diff-fret — Differentiable FRET modeling.
• diff-epr — Differentiable EPR/DEER simulation.
• synth-pdb — Synthetic structure generation.

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📖 Citation

@software{diff_hdx,
  author  = {Elkins, George},
  title   = {diff-hdx: Differentiable HDX-MS prediction in JAX},
  year    = {2026},
  url     = {https://github.com/elkins/diff-hdx},
  version = {0.1.0}
}

⚖️ License

MIT