Papers by Shayon Bhattacharya
Social Science Research Network, 2020
Neurodegenerative self-assembly of amyloid-forming peptides amyloid-beta42 (Ab42) and alpha-synuc... more Neurodegenerative self-assembly of amyloid-forming peptides amyloid-beta42 (Ab42) and alpha-synuclein (aS) through hydrophobic interactions is implicated in Alzheimer’s and Parkinson’s diseases, respectively. Although the native states of these peptide monomers are intrinsically disordered in water, their aggregation propensity have been correlated with the formation of short lived, partially folded helical conformers via helix-helix associations to helical oligomers, finally leading to formation of insoluble fibrils in vivo. Given the challenge in characterising the transient populations of helical intermediates by spectroscopy, little is known about what causes partially folded helical monomers of Ab42 and aS to be so aggregation-prone, compared to the fully folded helical or fully unfolded conformations. We comprehensively map the helical conformational sub-spaces of Ab42 and aS using extensive molecular dynamics computer simulations, utilizing a range of physical models. Our com...
Physical chemistry chemical physics : PCCP, 2019
The experimental finding that α-synuclein (αS) occurs physiologically as a helically folded tetra... more The experimental finding that α-synuclein (αS) occurs physiologically as a helically folded tetramer begs the question: why are helical tetramers the most populated multimers? While the helical tetramer is known to resist aggregation, the assembly mechanism of αS peptides remains largely unknown. By rationally designing a series of helical multimers from dimer to octamer, we characterized the free energy landscape of wild-type and mutated multimers using molecular dynamics computer simulations. Competition between supramolecular packing and solvation results in well-hydrated dimers and trimers, and more screened pentamers to octamers, with the helical tetramer possessing the most balanced structure with the lowest activation energy. Our data suggest that familial mutants are very sensitive to alterations in monomer packing that would in turn raise the energy barriers for multimerization. Finally, the hypothesis that the αS tetramer forms a soluble, benign "dead end" to cir...
Journal of Colloid and Interface Science
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Papers by Shayon Bhattacharya