Study on the disulfide bond and disulfide loop of native and mutated SOD1 protein.

The superoxide anions in the human body are reduced into hydrogen peroxide and molecular oxygen by the metallo enzyme Cu-Zn superoxide dismutase 1. The disulfide bond in SOD1 is essential to maintain the structural stability of protein and its proper folding. A computational study on the disulfide bond with the addition of residues was made using three different level of theories viz., B3LYP/6-31G (d,p), M052X/6-31G (d,p) and MP2/6-31G (d,p). The nature of disulfide bond was found to be unaffected with the additional residues being attached to the termini of cysteine residues. This result was found to be in agreement with the experimental values. The results of Molecular Dynamics simulation illustrate the crinkled appearance caused in the disulfide loop of A4V mutation. The conformational change in the disulfide loop was found to have significant effect on the loss of dimerization, metal binding affinity and overall protein stability. It is also noted that the disulfide loop with more number of residues is found to have no effect on the disulfide bond characteristics, but the disulfide loop with less number of residues is found to have remarkable effect for mutation in any position of the wild type protein.

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