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

AbstractSuperoxide 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. SarmaKeywords: SODserum albuminmolecular dynamicsdensity functional theorydocking Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThis study was funded by FAPERJ [grant E-26/210.134/2022; E-26/200.135/2023; E-26/010.001590/2019] and CNPq [grant 304105/2021-0]. grant E-26/210.134/2022 and E-26/200.135/2023 (FAPERJ): Camilo Henrique da Silva Lima. grant E-26/010.001590/2019 (FAPERJ) and grant 304105/2021-0 (CNPq): Sérgio de Paula Machado.