Analysis of the structural dynamics of the mutations in the kinase domain of PINK1 protein associated with Parkinson’s disease

•Mutational analysis of PINK1.•Characterizations of mutations.•Molecular dynamics simulations of PINK1 wild type and mutants.•PCA analysis of the MD data.•Prediction of the effects of the mutations. Parkinson’s disease (PD) is a very common neurodegenerative disorder and is considered to be one of the most severe disorders worldwide. Mutations in some PD causing genes are responsible for the early onset of the disease. Pathogenic variants in parkin, PINK1 and DJ1 genes can cause early-onset of PD. Many PINK1 gene mutations have been reported, but not all variants are pathogenic. The gene product of PINK1, also known as PINK1 protein, has 581 amino acid residues in it. Several different mutations are present throughout the kinase domain of PINK1 protein. In this work, we used in silico approaches to analyze the different types of mutations that are distributed in the kinase domain of the PINK1 protein. Based on our results, we categorized the mutations as high, moderate and low pathogenic variants. Furthermore, we performed molecular dynamics simulations of the pathogenic PINK1 variants to decipher their possible impacts on the structure and made a comparison with the wild type PINK1. In conclusion, we suggested the possible mechanistic roles of the pathogenic variants of PINK1 kinase domain that can affect its function. These pathogenic variants are the causative agents of early onset of PD called autosomal recessive Parkinson disease.