Although the folding of individual protein domains has been extensively studied both experimentally and theoretically, protein folding induced by a metal cation has been relatively understudied. Almost all folding mechanisms emphasize the role of the side-chain interactions rather than the peptide backbone in the protein folding process. Herein, we focus on the thermodynamics of the coupled metal binding and protein folding of a classical zinc-finger (ZF) peptide, using all-electron calculations to obtain the structures of possible nucleation centers and free energy calculations to determine their relative stability in aqueous solution. The calculations indicate that a neutral Cys first binds to hexahydrated Zn2+ via its ionized sulfhydryl group and neutral backbone oxygen, with the release of four water molecules and a proton. Another nearby Cys then binds in the same manner as the first one, yielding a fully dehydrated Zn2+. Subsequently, two His ligands from the C-terminal part of the peptide successively dislodge the Zn-bound backbone oxygen atoms to form the native-like Zn-(CYS)(2)(HiS)(2) complex. Each successive Zn complex accumulates increasingly favorable and native interactions, lowering the energy of the ZF polypeptide, which concomitantly becomes more compact, reducing the search volume, thus guiding folding to the native state. In the protein folding process, not only the side chains but also the backbone pepticle groups play a critical role in stabilizing the nucleation structures and promoting the hydrophobic core formation.