Background: The occurrence of Parkinson’s Disease (PD) is associated with the deposition
of proteinaceous aggregates formed by the self-assembly of α-synuclein protein. The pathogenesis of
PD has been reported to be linked with the α-synuclein gene. However, the presence of missense mutations:
A30P, A53T, E46K, H50Q, G51D and A53E has also been linked with the autosomal inheritance
of PD. Recently, it has been highlighted that C-terminal truncated α-synucleins undergo aggregation at a
faster rate while the full-length α-synucleins are critical.
Objective: To study the dimerization of C-terminal truncations of α-synuclein and its effect on the aggregation
Methodology: We investigated the dimerization of the two important C-terminal truncations (120 and
123) of α-synuclein using Molecular Dynamics Simulation and Potential of Mean Force (PMF) study.
Results: From our PMF study, we observed that the binding free energy value to be larger for the association
of C-terminal truncated α-synucleins than the value that has been reported for Wild-Type (WT)
in our earlier study.
Conclusion: Truncating the C-terminal region (which is considered to be intra-molecular chaperone) in
α-synucleins exposes the hydrophobic region and thereby increases the aggregation propensity.