Interactions of the amyloidogenic α-synuclein Protein with HSP12: A Molecular Dynamics Approach

Pandey, Ghanashyam (2021) Interactions of the amyloidogenic α-synuclein Protein with HSP12: A Molecular Dynamics Approach. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS Dissertation of Ghanashyam Pandey (16MS041)) 16MS041_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (2MB)

Abstract

α-synuclein (α-syn) ) Is a presynaptic neuronal protein, whose misfolding and aggregation causes α-synucleinopathy. Heat shock proteins (HSPs) are the major components of chaperone network preventing amyloid formation or helping proper folding. Striking similarities between HSP12 and α-synuclein led to molecular dynamics is a MD simulation study, here we investigate the effects of HSP12 in the α-synuclein (α-syn) oligomer, tetramer stability. We adopted an unique idea where, the sequence of α-synuclein (α-syn) i (outer or inner chain or both outer) of tetramer is replaced by the sequence of HSP12. Hence, 3 hybrid systems are simulated along with a native tetramer structure. Higher structural stability is observed in hybrid structures (AHSPP-B-C-D and AHSP-B-C-DHSP). Chains are found to interact strongly in hybrid systems. Analysis results showed that chains in hybrid systems form more inter- chain hydrogen bonds as compared to the native one and more contacts as compared to the native one which is losing it. Energetics data also suggest that AHSPP-B-C-D and AHSP-B-C-DHSP are more favorable.

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