Spectroscopy and Electron Transfer Dynamics of Blue Copper Proteins

Electron transfer is one of the most crucial reactions in biochemistry and the efficient and controlled transfer of electrons is crucial to living organisms. Metalloproteins with copper centres are particularly effective at performing electron transfer and understanding the link between structure and function of proteins lies at the heart of much biochemical and biophysical research. We propose a programme of research that interleaves novel theoretical developments (at Nottingham and Warwick) with new experiments (at Nottingham) to build a detailed understanding of the function of blue copper proteins, such as plastocyanin. Model complexes of the active site will be generated in the gas-phase and their spectroscopy measured. Adopting this approach will allow the oxidised and reduced forms of the active site to be studied directly, and will furnish information on how the presence of the coordinating ligands modulates the behaviour of the active site. Building on this, we plan to design complexes with tunable spectroscopic properties. The application of quantum chemical methods to study biological processes is without doubt an area of research that will grow rapidly in the near future. Molecular dynamics simulations within a quantum mechanics/molecular mechanics framework will be performed for the oxidised and reduced forms of the protein, and extended to the ligand-to-metal charge transfer state of the oxidised form. These simulations will form the basis for the development of force fields that will be used to study the charge transfer process and establish the form of the entatic state of the protein directly.

This proposal addresses a problem of fundamental biological importance. Blue copper proteins are crucial in processes such as photosynthesis, and this role coupled with their unusual spectroscopic properties has made them fascinating to researchers in both biology and chemistry. This is reflected in the large number of research publications concerning blue copper proteins. To date, the vast majority of spectroscopic work in these proteins has focused on the oxidised form. We propose to use model complexes as a basis to study both the oxidised and reduced forms, which are of equal importance for the redox chemistry of the protein. This work is interleaved with theoretical simulation of the dynamics of the protein and modelling of the charge transfer function of the proteins. Overall, this will elucidate the function of these proteins at an unprecedented level and will be of great interest to the large numbers of researchers working in this area. The research will yield outcomes of more general importance. The theoretical methods will establish a new approach to studying ab initio molecular dynamics simulations in an excited state and also provide new force fields that can be used to study the dynamics of these systems. More generally, the work will detail an approach to building force fields that can be applied to metalloproteins, which are prevalent throughout biology. Further afield, copper redox chemistry lies at the heart of 'Click chemistry', which is becoming of increasing importance in organic synthesis and drug discovery, and has an emphasis on efficient synthetic reactions with benign biproducts. Examining in detail the interaction of copper in different oxidation states with different ligands will provide physical insight into the chemical processes underpinning Click chemistry.