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Chemistry related to hydrogen/deuterium exchange-mass spectrometry (HDX-MS) for the analysis of proteins is described. First, the HDX rates of various functional groups in proteins are explained by reviewing the observed rates described in the literature, followed by estimating rates of all types of heteroatom hydrogens in proteins using proton transfer theory and the pKa values. The estimated HDX rates match well with the respective observed rates for most functional groups, with the exception of indole and amide groups. The discrepan