A Residue-Resolved Bayesian Approach to Quantitative Interpretation of Hydrogen-Deuterium Exchange from Mass Spectrometry: Application to Characterizing Protein-Ligand Interactions.

ABSTRACT: Characterization of interactions between proteins and other molecules is crucial for understanding the mechanisms of action of biological systems and, thus, drug discovery. An increasingly useful approach to mapping these interactions is measurement of hydrogen/deuterium exchange (HDX) using mass spectrometry (HDX-MS), which measures the time-resolved deuterium incorporation of peptides obtained by enzymatic digestion of the protein. Comparison of exchange rates between apo- and ligand-bound conditions results in a mapping of the differential HDX (ΔHDX) of the ligand. Residue-level analysis of these data, however, must account for experimental error, sparseness, and ambiguity due to overlapping peptides. Here, we propose a Bayesian method consisting of a forward model, noise model, prior p

SUBMITTER: Saltzberg DJ 

PROVIDER: S-EPMC5693600 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature