DFT calculations of copper complexes mimicking superoxide dismutase and docking studies and molecular dynamics of the transition metal complex binding to serum albumin

Superoxide dismutase (SOD) is a metalloenzyme whose antioxidant activity is mimicked by some transition metal complexes, and such ability can be added in proteins such as the bovine serum albumin (BSA), creating a hybrid protein. In this work, density functional theory (DFT) calculations of three Cu(II)-complexes of general formula [CuL2phen] (phen = phenanthroline; C1, L = mefenamate; C2, L = tolfenamate; C3, L = flufenamate) with SOD-like activity, and docking and molecular dynamics (MD) simulations of these complexes with the BSA were performed. The DFT calculations revealed that the complex reduction involves Cu(II) -> Cu(I) reduction, the theoretical electron affinity (EA) correlated with the SOD-like activity (IC50), and the contribution of the phenanthroline ligand and the metal in LUMO it's related with the complex-protein interaction (KVS). The docking and MD simulations revealed the binding site of the complexes in BSA and the residues involved in the binding. The stability of the Cu(II) and Cu(I) forms of the complexes in the site indicated that the catalysis promoted by these complexes occurs in the same region of the BSA and that their mimetic activity can be incorporated into BSA, creating a hybrid protein (BSA with SOD activity)Communicated by Ramaswamy H. Sarma

Automated summary

In this study, the interactions between Cu(II) complexes with SOD-like activity and BSA were investigated using computational, docking, and molecular dynamics simulations. The results revealed the binding site and residues involved in the interaction. The theoretical calculations showed that the reduction of the complexes involved Cu(II)->Cu(I) reduction and the electron affinity correlated with the SOD-like activity. The docking and simulations demonstrated stable binding of the complexes in BSA and their mimetic activity in the same catalytic region.