Molecular-dynamics calculations, zinc

Finally, a DEER study on models for molecular wires made from butadiyne-linked zinc porphyrin oligomers, end-labeled with nitroxide radicals, was performed by Lovett, Anderson, and coworkers [107]. Unlike in [104—106], one can control the conformations of these metalloporphyrin-based strucmres by self-assembly with multidentate amine ligands, which bend the rigid oligomeric structure. The experimentally found end-to-end distances in these complexes match the predictions from molecular dynamics calculations. This study thus presents a proof-of-principle that DEER spectroscopy is also well suited for understanding more complex supramolecular stmctures. 

Calculations pertaining to the mechanism of action of metallo-/ -lactamases have been performed for the mono-zinc -lactamase of Bacillus cereus as well as on the binuclear P -lactamase of Bacteroidesfragilis. Molecular-dynamics and quantum-mechanical... 

However, details of this process including the mode of urea binding, the protonation state of individual surround protein residues, and the exact identity of the nucleophile are still under debate. Cyanate also was proposed as a possible intermediate in the urease mechanism (33). Recent quantum chemical calculations and molecular dynamics simulations indicated that hydrolytic and ehmination mechanisms might indeed compete, and that both are viable reaction channels for urease (34—37). Finally, an important issue is Why does urease require nickel as the metal of choice, whereas most other metallohydrolases use zinc While it was speculated that, inter alia, the relatively rigid and stable coordination environment around the Ni(II) ions as opposed to the higher kinetic lability and lower thermodynamic stability of Zn(II) complexes might play a role (31), this fundamental question has not yet been answered. 

As observed in other systems, the obvious difficulty in elucidating reaction mechanisms based on static structural snapshots subsequently initiated structural-dynamic theoretical studies of metalloproteinases. The active site chemistry of zinc-dependent enzymes has been studied using a variety of theoretical approaches. For example, mixed quantum mechaiucal/molecular calculations and classical molecular dynamic simulations have been employed, especially studies using density functional methods on redox-active metal centers (42). 

In another recent study of dielectric properties of a protein-water system, Loeffler et al. ° presented a rigorous derivation of a theory for the calculation of the frequency-dependent dielectric properties of each component of a system which, in their example, consisted of the HIV-1 zinc finger peptide, water, and one zinc and two chloride ions. A 13.1 ns molecular dynamics simulation was performed, and, from it, dielectric constants for the various components of the system were extracted. It was discovered that the first hydration layer had a much lower dielectric response (47) than that of ordinary bulk water (80). The... 

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