Understanding specific ion effects on proteins
remains a considerable challenge. N-methylacetamide serves as a
useful proxy for the protein backbone that can be well characterized
both experimentally and theoretically. The spectroscopic signatures
in the amide I band reflecting the strength of the interaction of alkali
cations and alkaline earth dications with the carbonyl group remain
difficult to assign and controversial to interpret. Herein, we directly
compute the infrared (IR) shifts corresponding to the binding of
either sodium or calcium to aqueous N-methylacetamide using ab
initio molecular dynamics simulations. We show that the two cations
interact with aqueous N-methylacetamide with different affinities 
and in different geometries. Because sodium exhibits a weak
interaction with the carbonyl group, the resulting amide I band 
is similar to an unperturbed carbonyl group undergoing aqueous
solvation. In contrast, the stronger calcium binding results in 
a clear IR shift with respect to N-methylacetamide in pure water.