Potential of Mean Force study on the dimerization of non-amyloid-β component of Human α-Synuclein
Self-association of α-Synuclein monomers into oligomeric species and highly ordered amyloid fibrils is linked to Parkinson’s disease (PD). The peptide fragment corresponding to region 61-95 of α-synuclein protein originally termed as non-amyloid β component (NAC) has been suggested to play a critical role in the fibrillation process. To better understand the early events of aggregation process, inter-molecular interactions between the two NAC regions during the formation of dimer is critical. Here we demonstrate the molecular dynamics and potential of mean force (PMF) techniques to study the parallel and anti-parallel dimers of the peptide corresponding to the 71-82 (71VTGVTAVAQKTV82) region of α-synuclein. From the PMF study, we noticed two basins of attraction, one at 10 Ǻ and 14 Ǻ for the parallel and only one basin near 12 Ǻ for the anti-parallel conformation of the dimer of the peptide. From docking study using SymmDock, we noticed higher side chain interactions and interface surface area for the anti-parallel conformation of the dimer of the peptide. Our results thus provide atomistic insights into the structural features of the core fibril forming NAC region during dimerization which may open the way to explore the molecular basis of this disease.
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