HRaDeX: R Package and Web Server for Computing High-Resolution Deuterium Uptake Rates for HDX-MS Data.

Abstract

Hydrogen-deuterium exchange monitored by mass spectrometry (HDX-MS) is a well-established and powerful technique used to study protein dynamics and stability by capturing local and global unfolding events in protein structures. However, in this technique, obtaining region-specific information requires proteolytic digestion that breaks the protein into peptide fragments, causing the HDX data to reflect averages over these fragments rather than individual amino acids. We propose a new computational method that provides deuterium uptake kinetic parameters with high resolution, considering deuterium uptake trajectories of superimposed peptides. Our algorithm, HRaDeX, is available as a web server and an R package capable of processing data from single-state and comparative HDX-MS studies. Utilizing eight benchmark data sets, we demonstrate that HRaDeX reaches an average root-mean-square error of 7.15% in the reconstitution of experimental normalized deuterium uptake curves.