Background and objective: Mutations in the SOD1 protein can lead to the death of motor neurons, which, in turn, causes an incurable disease called amyotrophic lateral sclerosis (ALS). At the same time, the mechanism of the onset and development of this disease is not fully understood and is often contradictory.
Methods: Accelerated Molecular Dynamics as implemented in the OpenMM library, principal component analysis, regression analysis, random forest method.
Results: The stability of hydrogen bonds in 72 mutants of the SOD1 protein was calculated. Principal component analysis was carried out. Based on ten principal components acting as predictors, a multiple linear regression model was constructed. An analysis of the correlation of these ten principal components with the initial values of the stability of hydrogen bonds made it possible to characterize the contribution of known structurally and functionally important sites in the SOD1 to the scatter of ALS patients' survival time.
Conclusion: Such an analysis made it possible to put forward hypotheses about the relationship between the stabilizing and destabilizing effects of mutations in different structurally and functionally important regions of SOD1 with the patients's survival time.
Keywords: Amyotrophic lateral sclerosis; Hydrogen bonds; Principal component analysis; Regression models; SOD1 mutations; Survival time prediction.
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