MOLECULAR-DYNAMICS STUDIES ON SUPEROXIDE-DISMUTASE AND ITS MUTANTS - THE STRUCTURAL AND FUNCTIONAL-ROLE OF ARG-143

Molecular dynamics (MD) calculations have been performed on superoxide dismutase (SOD) and on its mutants on the Arg 143 residue, which has been modified to a Glu and to a Ile residue. The simulations were performed over the entire "orange" subunit, solvated by about 3300 water molecules, and on the atoms at the subunit-subunit interface. A 10-angstrom residue-based cut-off for the pair interactions was used. The trajectories were calculated for 63 ps, and the last 36 ps were used for structural analysis. The set of parameters used for describing the metal ions reproduces fairly well the structure of the active site. Significantly, the semicoordinated water molecule maintains its position close to the copper ion, although in the simulation no bond has been imposed between it and the copper ion, in agreement with experimental evidence. In the wild type SOD, the active site channel shows high mobility, resulting in an increase of the open section. In particular Arg 143 is highly mobile. On the contrary, the mutants show a reduced mobility at the channel, the decrease being larger when a negative group, such as a Glu, is present on position 143 with respect to a neutral group as Ile. This behavior is related to the catalytic activity of SOD and its mutants here investigated, and a role of the extent of the mobility of the residues hanging in the active site channel on the enzymatic reaction is proposed.