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 experim ental data. Such calibrations have been carried out for biologically import ant zinc-cysteinate complexes in this work. Calculations using different qu antum mechanical methods were carried out to determine the theory/basis set that can reproduce the X-ray structure of a zinc-cysteinate-like complex a nd 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 bon d distance of 2.34 Angstrom for bis-(ethane-1,2-dithiolato-S,S')-zine(II) a nd [Zn(CH3S-)(4)](2-), in excellent agreement with experiment. In contrast, B3-LYP with the same basis set overestimated the average Zn-S bond distanc e 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 ener gy 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 w ell 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 hel p in modeling the structural and thermodynamical properties of zinc-cystein ate binding sites. Moreover, the strategy described in this work could be a pplied in modeling other metal-binding sites in proteins.