Copper Oxidation/Reduction in Water and Protein: Studies with DFTB3/MM and VALBOND Molecular Dynamics Simulations

Abstract

We apply two recently developed computational methods, DFTB3 and VALBOND, to study copper oxidation/reduction processes in solution and protein. The properties of interest include the coordination structure of copper in different oxidation states in water or in a protein (plastocyanin) active site, the reduction potential of the copper ion in different environments, and the environmental response to copper oxidation. The DFTB3/MM and VALBOND simulation results are compared to DFT/MM simulations and experimental results whenever possible. For a solvated copper ion, DFTB3/MM results are generally close to B3LYP/MM with a medium basis, including both solvation structure and reduction potential for Cu(II); for Cu(I), however, DFTB3/MM finds a two-water coordination, similar to previous Born-Oppenheimer molecular dynamics simulations using BLYP and HSE, while B3LYP/MM leads to a tetrahedron coordination. For a tetra-ammonia copper complex in solution, VALBOND and DFTB3/MM are consistent in terms of both structural and dynamical properties of solvent near copper for both oxidation states. For copper reduction in plastocyanin, DFTB3/MM simulations capture the key properties of the active site, and the computed reduction potential and reorganization energy are in fair agreement with experiment, especially when periodic boundary condition is used. Overall, the study supports the value of VALBOND and DFTB3(/MM) to the analysis of fundamental copper redox chemistry in water and protein, and the results also help highlight areas where further improvements in these methods are desirable.

A QM/MM study of the nature of the entatic state in plastocyanin

“…In this state, the protein has a rich spectroscopy, and has been studied by several different spectroscopic techniques including electronic absorption, circular dichroism, magnetic circular dichroism, and x‐ray absorption spectroscopies . Alongside these experimental measurements there have been numerous theoretical studies with a wide variety of different levels of approximation . These studies have led to an understanding of the nature of the observed spectroscopic features and detailed insight into the electronic structure of the active site.…”

“…Deeth studied the oxidized form of a range of blue copper proteins, including plastocyanin, with ligand field molecular mechanics (LFMM) and found an entatic strain energy of about 10 kcal mol −1 . Further hybrid quantum mechanics/molecular mechanics (QM/MM) approaches and implicit models of the protein environment have been used to obtain optimized geometries of each state.…”

Reactive molecular dynamics: From small molecules to proteins

“…Both processes can be cast within the framework of MS-ARMD 67,234 but alternative techniques have also been employed. Typical applications are the investigation of the change in the solvent structure around metal-complexes [235][236][237][238][239] or the spectroscopic signatures accompanying proton transfer, 68,69,[240][241][242][243][244][245] or the energetics of proton transfer in proteins. 246 A field by itself is the investigation of proton transfer in bulk water for which a myriad of FF-based techniques have been developed.…”

Design and interaction mechanism of ligand targeted with folate receptor α and β

“…A comprehensive description of the method can be found in the literature . It has been found that this method is successful for predicting the binding structure of biomolecule complexes involving weak interaction systems and has already been used to study the binding of biomolecules . In this work, we used the conjugate gradient algorithm for the structure optimizations, with the force convergence criterion set at 10 −4 au and the charge convergence criterion set to 10 −4 electrons.…”