Investigation of point mutations on the structure of human SOD۱ enzyme by molecular dynamics simulation

Superoxide dismutase ۱ (SOD۱) is an antioxidant enzyme. Mutation in superoxide dismutase ۱ (SOD۱) causes amyotrophic lateral sclerosis (ALS). Therefore, in this study, the conformational and dynamic changes of the mutant protein were investigated. The crystallographic structure of wild-type SOD۱ code ۲C۹V was retrieved from the Protein Database (PDB). The G۴۱D and L۳۸R mutations were then created on the file. In this method, the interactions between atoms and molecules at the location and velocity of each atom at intervals of ۵ nano seconds were calculated using GROMACS software. Using the root mean square deviation, the mean accuracy of the simulation was investigated and with the help of various other analyzes, including the study of changes in the radius of gyration and the calculating of the number of hydrogen bonds, we observed that mutations have a significant effect on protein structure. The mean change curve of hydrogen bonds for G۴۱D and L۳۸R mutants are ۱۰۶ and ۱۰۳ versus ۱۰۰ hydrogen bonds for wild-type protein, respectively. These changes, however small, are effective in reducing the flexibility of the G۴۱D. For the L۳۸R mutant, these changes are almost identical to the wild-type form. The results of the radius of gyration show that in the G۴۱D mutant the protein structure is more compact than in the wild-type. The results of RMSF in G۴۱D and L۳۸R mutants in the ۸۰-۷۰ and ۱۱۵-۱۰۵ regions showed a decrease in the amount of RMSF compared to the wild-type enzyme, indicating that the mutants were less flexible than the wild-type protein. The results of molecular dynamics of this study show that the occurrence of mutations in loop ۳ and β۴ in SOD۱ protein causes slight conformational changes in the mutated regions, so that according to these local changes, the G۴۱D mutant is more stable and compact than the L۳۸R mutant.

کلیدواژه ها:

G۴۱D mutant enzyme ، L۳۸R mutant enzyme ، RMSD ، Radius of gyration