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Current Chemical Biology


ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Research Article

Dimerization of C-terminal Truncations of α-synuclein and its Effect on the Aggregation Propensity: A Potential of Mean Force Study

Author(s): Airy Sanjeev and Venkata Satish Kumar Mattaparthi*

Volume 12, Issue 2, 2018

Page: [191 - 200] Pages: 10

DOI: 10.2174/2212796812666180430143502

Price: $65


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 propensity.

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.

Keywords: Disordered, parkinson's disease, truncation, molecular dynamics, potential of mean force, α- synuclein.

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