Background
Parkinson's disease (PD) is the most prevalent neurodegenerative condition in humans that impairs mobility and affects movement. Oxidative stress has been recognised as one of the major factors contributing to the development of PD. An organism's ability to withstand oxidative stress and appropriately eliminate free radicals is known to depend on the activity of antioxidant enzymes such as superoxide dismutases (SODs). Genetic polymorphism of SOD enzymes may influence protein functionality and consequently impact the enzyme's ability to reduce oxidative damage. With possible links between SOD functionality, the level of oxidative stress and the onset and course of PD development, this work aims to discover and characterise the impact of SOD1 gene variations on protein structure that can negatively affect enzyme activity and potentially increase the likelihood of PD development.
 Method
In silico methods were applied to analyse publicly available databases (NCBI and UniProt) using tools available via Galaxy (https://usegalaxy.org.au/). The workflow steps included the following: (1) data retrieval for SOD1 gene sequence and its variants, (2) SOD1 variant filtering to identify the variants, (3) comparison of the predicted protein structures that would result from translation of the variants to the wild-type SOD1 protein, and (4) identification of the most deleterious variants.
Results
Genetic polymorphism variability among the 3,456 SOD1 gene variants across all databases included missense, synonymous, and frameshift variants, with missense variants being the most prevalent. Based on SnpEff variation impact projections and clinically significant NCBI data, 13 out of 80 variants were projected to have the most detrimental effect on enzyme activity. These thirteen variants were assessed further using InterProScan and Swiss-Model regarding expected effects on the structure and function of the SOD1 protein. The frameshift and missense variations were the most damaging mutations to the predicted protein structure, leading to the loss of significant domains or major alterations in the predicted SOD1 proteins' domains.
Conclusions
Our research adds to the body of information about genetic SOD polymorphism and provides a summary of the in silico implications on functional domains and potential effects on oxidative stress-related disorders like Parkinson's disease. Specific SOD protein variants that are probably detrimental were identified by in silico analysis. Additional follow-up case-control studies are required to evaluate the presence of the identified SOD1 variants in the PD population and determine whether those specific variants increase oxidative stress status and increase the risk of PD development or speed up the disease progression.