  The zinc finger structure where a Zn2+ ion binds to 4 cysteine or histidine
amino acids in a tetrahedral structure is very common motif of nucleic acid
binding proteins. The corresponding interaction model is present in 3% of the
genes of human genome. As a result, zinc finger has been shown to be extremely
useful in various therapeutic and research capacities, as well as in
biotechnology. In stable configuration, the cysteine amino acids are
deprotonated and become negatively charged. This means the Zn2+ ion is
overscreened by 4 cysteine charges (overcharged). It is question of whether
this overcharged configuration is also stable when such negatively charged zinc
finger binds to negatively charged DNA molecule. Using all atom molecular
dynamics simulation up to microsecond range of an androgen receptor protein
dimer, we investigate how the deprotonated state of cysteine influences its
structure, dynamics, and function in binding o DNA molecules. Our results show
that the deprotonated state of cysteine residues are essential for mechanical
stabilization of the functional, folded conformation. Not only this state
stabilizes the protein structure, it also stabilizes the protein-DNA binding
complex. The differences in structural and energetic properties of the two
(sequence-identical) monomers are also investigated showing the strong
influence of DNA on the structure of zinc fingers upon complexation. Our result
has potential impact on better molecular understanding of one of the most
common classes of zinc fingers
