Simulations based on perfectly funneled energy landscapes often capture many of the kinetic features of protein folding. We examined whether simulations based on funneled energy functions can also describe fluctuations in native-state protein ensembles. We quantitatively compared the site-specific local stability determined from structure-based folding simulations, with hydrogen exchange protection factors measured experimentally for ubiquitin, chymotrypsin inhibitor 2, and staphylococcal nuclease. Different structural definitions for the open and closed states based on the number of native contacts for each residue, as well as the hydrogen-bonding state, or a combination of both criteria were evaluated. The predicted exchange patterns agree with the experiments under native conditions, indicating that protein topology indeed has a dominant effect on the exchange kinetics. Insights into the simplest mechanistic interpretation of the amide exchange process were thus obtained.