ANALYSING THE INVOLVEMENT OF A CU/ZN SUPEROXIDE DISMUTASE MUTATION IN FAMILIAL AMYOTROPHIC LATERAL SCLEROSIS USING MOLECULAR DYNAMICS SIMULATION TECHNIQUE

Abstract

Amyotrophic lateral sclerosis (ALS) is a type of neuro-degenerative disorder that causes muscle weakness, many type of disabilities and can eventually lead to death. Out of all the worldwide Amyotrophic lateral sclerosis cases, 5 to 10% are Familial Amyotrophic lateral sclerosis (FALS) cases. The involvement of superoxide dismutase (SOD1) in Familial Amyotrophic Lateral Sclerosis can be found in many published literatures. I tool a missense mutation of SOD1 gene which causes the substitution of Threonine (Thr) for Alanine (Ala) at the 5th position and analysed its involvement in FALS using molecular dynamics simulation technique. To serve the purpose we first designed the mutant protein i.e. mutant Cu/Zn superoxide dismutase (m4B3E) using homology modeling software SWISS MODEL and analysed stability of the same against the wild type protein i.e. Cu/Zn superoxide dismutase (4B3E) by using molecular dynamics simulation as a tool. I analysed the behavior of the mutant protein and wild type protein simultaneously, as the wild type protein is experimentally proven it is conceded stable. So, I compared the mutant protein to the wild type in the conditions similar to the in vivo environment as molecular dynamics simulation mimics the in vivo environment. We analysed the results in terms of RMSD, RMSF and radius of gyration, further visualization of the simulation was done using VMD (Visual Molecular Dynamics) tool.