PyHDX

PyHDX computes residue-level Gibbs free energy changes (ΔG) from Hydrogen–Deuterium Exchange Mass Spectrometry (HDX-MS) data to quantify intrinsic protein dynamics and enable comparative analyses across states, oligomeric assemblies, and homologues.

Key Features:

• Residue-Level Analysis: Provides ΔG values at amino-acid resolution derived from HDX-MS to report intrinsic protein dynamics.
• Universal ΔG Metric: Uses Gibbs free energy changes (ΔG) as a standardized measure to quantify and compare protein flexibility across conditions and sequences.
• Batch Processing Capability: Performs batch extraction of ΔG across multiple datasets, protein conditions, and homologues.
• Relation to Normal Modes: Produces ΔG values that are directly related to protein normal modes to support cross-protein comparison of flexibility.
• Overcomes Peptide-Based Limitations: Extracts intrinsic residue-level dynamics beyond traditional peptide-based HDX-MS analyses to facilitate cross-comparison.

Scientific Applications:

• Structural biology: Maps intrinsic residue-level flexibility to interpret protein conformational landscapes.
• Comparative dynamics: Enables standardized comparisons of dynamics between homologous sequences and different oligomeric assemblies.
• Ligand- and state-specific analysis: Quantifies differential dynamics induced by ligand binding or changes in protein state.

Methodology:

Computational algorithms process HDX-MS data to extract residue-level Gibbs free energy changes (ΔG), perform batch extraction across conditions, and relate ΔG values to protein normal modes.