Quantum Chemical Studies of Reactions of the Cyclic Disulfides with the Zinc Finger Domains in the HIV-1 Nucleocapsid Protein (NCp7)

By using quantum chemistry methods, including ab initio Hartree−Fock (HF), as well as the Density Functional Theory approach employing B3LYP approximation, the reaction profiles of three cyclic disulfide species with model zinc finger domains in the HIV-1 nucleocapsid protein (NCp7) have been analyzed. It is shown that the disulfide molecules can act as efficient agents destroying the tetrahedral coordination sphere of the zinc finger domains. The consequence of the reaction is a break of one of the Zn−S bonds and removal of the corresponding molecular thiolate group from the domain by forming a new S−S bond between sulfur atoms from the withdrawing fragment and of the electrophilic agent. As a result of this process the zinc-containing site transforms from the initial tetrahedral geometry to a planar geometry configuration. This transformation further facilitates destruction of the metal binding site. The calculations explicitly show correlations between redox potentials of the electrophilic agents, their reactivity, and barrier heights on the reaction pathway.