  Zinc-fingers, which widely exist in eukaryotic cell and play crucial roles in
life processes, depend on the binding of zinc ion for their proper folding. To
computationally study the zinc coupled folding of the zinc-fingers, charge
transfer and metal induced protonation/deprotonation effects have to be
considered. Here, by attempting to implicitly account for such effects in
classical molecular dynamics and performing intensive simulations with explicit
solvent for the peptides with and without zinc binding, we investigate the
folding of the Cys2His2 type zinc-finger motif and the coupling between the
peptide folding and zinc binding. We find that zinc ion not only stabilizes the
native structure, but also participates in the whole folding process. It binds
to the peptide at early stage of folding, and directs or modulates the folding
and stabilizations of the component beta-hairpin and alpha-helix. Such a
crucial role of zinc binding is mediated by the packing of the conserved
hydrophobic residues. We also find that the packing of the hydrophobic residues
and the coordination of the native ligands are coupled. Meanwhile, the
processes of zinc binding, mis-ligation, ligand exchange and zinc induced
secondary structure conversion, as well as the water behaviour, due to the
involvement of zinc ion are characterized. Our results are in good agreement
with related experimental observations, and provide significant insight into
the general mechanisms of the metal-cofactor dependent protein folding and
other metal induced conformational changes of biological importance.
