HDXer

HDXer computes hydrogen–deuterium exchange (HDX) behavior from structural ensembles and employs ensemble reweighting to interpret HDX-MS experiments for inference of protein conformational dynamics.

Key Features:

• H-D Exchange Rate Calculation: HDXer computes hydrogen–deuterium exchange rates for each structure in a candidate ensemble derived from molecular dynamics simulations or other structural sources.
• Ensemble Reweighting (maximum-entropy): Employs a maximum-entropy biasing scheme to reweight conformational populations so that computed HDX matches experimental HDX-MS data within a specified error margin.
• Integration of simulation and experimental data: Correlates microscopic dynamics from simulations with macroscopic HDX-MS exchange behavior to enable objective interpretation of experimental observations.

Scientific Applications:

• Protein structure and dynamics analysis: Interprets HDX-MS data to probe protein folding, conformational changes, and dynamic behavior at the molecular level.
• Mapping conformational changes and folding: Links per-structure exchange rates to ensemble populations to identify regions undergoing folding or conformational transitions.
• Characterizing interactions: Detects protection changes in HDX patterns to study ligand binding and protein–protein interaction-induced conformational effects.

Methodology:

HDXer calculates per-structure hydrogen–deuterium exchange rates from molecular simulations or other structural ensembles and applies a maximum-entropy ensemble reweighting to adjust conformational weights to reproduce HDX-MS experimental data within a specified error margin.