Molecular dynamics simulations of the enzyme Cu, Zn superoxide dismutase

The enzyme Cu, Zn superoxide dismutase (Cu,Zn-SOD) is a ubiquitous oxireductase, which is responsible for the cellular defense against oxidative stress caused by the high toxicity of the superoxide radical, and has been also linked to some cases of familiar amyotrophic lateral sclerosis. In the present study a set of molecular mechanics parameters for the active site of Cu,Zn-SOD has been derived. Afterward, an extensive molecular dynamics simulation has been carried out in an aqueous environment. The obtained results shed a further light on the structural flexibility of the backbone, where the active site is nested, and the solvation shell occupancy. The relatively small backbone deviation, shown by a root-mean-square deviation below 1.0 A, confirms the accuracy of the parameters. The solvent shell analysis has shown that the first solvation shell is located at about 5 A from the copper ion, generating an empty cavity with enough space to accommodate the superoxide radical. The low residence time means that a high permutation rate of water molecules in both solvation shells is consistent with the efficiency of this catalytic mechanism. Hybrid studies using ONIOM methodologies can now be done to evaluate the mechanistic implications of the explicit inclusion of the whole system.