Modeling Zn2+-cysteinate complexes in proteins

Before computational results can be reliably interpreted, it is critical to calibrate the theoretical calculations with respect to appropriate experimental data. Such calibrations have been carried out for biologically important zinc-cysteinate complexes in this work. Calculations using different quantum mechanical methods were carried out to determine the theory/basis set that can reproduce the X-ray structure of a zinc-cysteinate-like complex and the measured gas-phase deprotonation free energy of H2S. The S-VWN/6-311++G(d,p) method was found to reproduce the X-ray geometry of bis-(ethane-1,2-dithiolato-S, S')-zinc(II). In particular, it yielded an average Zn-S bond distance of 2.34 Angstrom for bis-(ethane-1,2-dithiolato-S,S')-zine(II) and [Zn(CH3S-)(4)](2-), in excellent agreement with experiment. In contrast, B3-LYP with the same basis set overestimated the average Zn-S bond distance by about 0.1 Angstrom. With the 6-311++G(d,p) basis set, MP2 and post-MP2 methods could reproduce the experimental gas-phase deprotonation free energy of H2S, while DFT methods such as B3-LYP and S-VWN yielded less accurate values. Furthermore, a set of effective radii for zinc and atoms of water and HS- consistent with S-VWN/6-311++G(d,p) geometries and NBO charges as well as MP2/6-311 ++G(d,p)//S-VWN/6-311++G(d,p) energies has been obtained. These radii predicted the correct free energy of Zn2+ binding to dianionic 2,3-dimercapto-1-propanol in solution. The results obtained here should help in modeling the structural and thermodynamical properties of zinc-cysteinate binding sites. Moreover, the strategy described in this work could be applied in modeling other metal-binding sites in proteins.