Hydrogen-deuterium exchange (HDX) experiments are widely used in studies of protein dynamics. To predict the propensity of amide hydrogens for exchange with deuterium, several models have been reported in which computations of amide-hydrogen protection factors are carried out using molecular dynamics (MD) simulations. Given significant variation in the criteria used in different models, the robustness and broader applicability of these models to other proteins, especially homologous proteins showing distinct amide-exchange patterns, remains unknown. The sensitivity of the predictions when MD simulations are conducted with different force-fields is yet to tested and quantified. Using MD simulations and experimental HDX data on three homologous signaling proteins, we report detailed studies quantifying the performance of seven previously reported models (M1-M7) of two general types: empirical and fractional-population models. We find that the empirical models show inconsistent predictions but predictions of the fractional population models are robust. Contrary to previously reported work, we find that the solvent-accessible surface area of amide hydrogens is a useful metric when combined with a new metric defining the distances of amide hydrogens from the first polar atoms in proteins. On the basis of this, we report two new models, one empirical (M8) and one population-based (M9). We find strong protection of amide hydrogens from solvent exchange both within the stable helical motifs and also in the interhelical loops. We further observe that the exchange-competent states of amide hydrogens occur on the sub 100 ps time-scale via localized fluctuations, and such states among amides of a given protein do not appear to show any cooperativity or allosteric coupling.