Insights into the structural and functional analysis of impact of the missense mutations on α-synuclein: an in silico study

Abstract

Abstract Background Alpha synuclein (α-synuclein) is coded by SNCA gene and found in a helical form with phospholipids or in an unfolded arrangement in the cytosol and belongs to the synuclein family other than beta synuclein and gamma synuclein. It is a short protein made of 140 amino acids with three domains: an N-terminal lipid binding helix, a non-amyloid-ß component (NAC), and an acidic tail at the C-terminus. α-Synuclein is present in aggregated and fibrillar form in Lewy bodies and its association has been related to multiple system atrophy (MSA), Parkinson’s disease (PD), and Dementia with Lewy bodies (DLB). Our objective is to investigate and prioritise the possible nsSNPs in the α-synuclein protein that have been potentially connected to human neurodegenerative diseases. Results We used the series of computational tools to predict the mutation's harmful effect on three-dimensional structure of α-synuclein based on consensus approach. Our findings pointed to a significant computational blueprint for discovering nsSNPs connected to neurodegenerative illnesses from a large SNP data set while also minimising the expenses of experimentally showing harmful nsSNPs. Conclusions The prioritised G25S (rs1433622151), V66E (rs1261243630), and V77D (rs745815563) mutations can be employed in additional experimental studies to assess the α-synuclein protein mutation in relation to neurodegenerative illnesses and develop a therapeutics against them. Graphical Abstract