The extent to which proteins are protected from hydrogen deuterium exchange (HDX) provides valuable insight into their folding, dynamics and interactions. Characterised by mass spectrometry (MS), HDX benefits from negligible mass restrictions and exceptional throughput and sensitivity but at the expense of resolution. Exchange mechanisms which naturally transpire for individual residues cannot be accurately located or understood because amino acids are characterised in differently sized groups depending on the extent of proteolytic digestion. Here we report HDXmodeller, the world's first online webserver for high-resolution HDX-MS. HDXmodeller accepts low-resolution HDX-MS input data and returns high-resolution exchange rates quantified for each residue. Crucially, HDXmodeller also returns a set of unique statistics that can correctly validate exchange rate models to an accuracy of 99%. Remarkably, these statistics are derived without any prior knowledge of the individual exchange rates and facilitate unparallel user confidence and the capacity to evaluate different data optimisation strategies.
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