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Proteins are the workhorses of life, and their biological function is
intimately associated with their structure and dynamical behavior. Indeed,
minute perturbations to their intrinsic properties may cause them to
become dysfunctional and may trigger the onset of debilitating diseases.
However, despite the emergence of advanced experiments, unraveling protein
(and biomolecular) behavior at the ‘single molecule’ level remains a
challenging task. In recent times, computer simulation methods have
emerged as powerful tools to probe biomolecular behavior, and thereby gain
key insights into their structural propensities, dynamics, and self- and
co-assembly under
various conditions. In this talk, I will highlight some of our recent
efforts on unraveling the molecular origins of proteopathies, such as
Alzheimer’s disease, that are triggered by protein assembly and
aggregation. Our work has focused on the early oligomerization mechanisms
in the Amyloid β peptide; its co-assembly with another disease
associated protein, αSynuclein; and a mechanistic understanding of
how the pathways of assembly may be potentially modulated. I will also
present our preliminary investigations into the origins of the anomalous
process of protein cold
denaturation, and how stochastic perturbations may trigger pathogenenic
transformations in normally folded proteins.
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