@article { ISI:000345641400039,
	title = {Non-uniform early structural response of globular proteins to cold denaturing conditions: a case study with Yfh1},
	journal = {Journal of Chemical Physics},
	volume = {141},
	number = {20},
	year = {2014},
	month = {NOV},
	pages = {205103},
	publisher = {AMER INST PHYSICS},
	type = {Article},
	address = {CIRCULATION \& FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA},
	abstract = {<p>The mechanism of cold denaturation in proteins is often incompletely understood due to limitations in accessing the denatured states at extremely low temperatures. Using atomistic molecular dynamics simulations, we have compared early (nanosecond timescale) structural and solvation properties of yeast frataxin (Yfh1) at its temperature of maximum stability, 292 K (T-s), and the experimentally observed temperature of complete unfolding, 268 K (T-c). Within the simulated timescales, discernible {\textquoteleft}{\textquoteleft}global{\textquoteright}{\textquoteright} level structural loss at T-c is correlated with a distinct increase in surface hydration. However, the hydration and the unfolding events do not occur uniformly over the entire protein surface, but are sensitive to local structural propensity and hydrophobicity. Calculated infrared absorption spectra in the amide-I region of the whole protein show a distinct red shift at T-c in comparison to T-s. Domain specific calculations of IR spectra indicate that the red shift primarily arises from the beta strands. This is commensurate with a marked increase in solvent accessible surface area per residue for the beta-sheets at T-c. Detailed analyses of structure and dynamics of hydration water around the hydrophobic residues of the beta-sheets show a more bulk water like behavior at T-c due to preferential disruption of the hydrophobic effects around these domains. Our results indicate that in this protein, the surface exposed beta-sheet domains are more susceptible to cold denaturing conditions, in qualitative agreement with solution NMR experimental results. (C) 2014 AIP Publishing LLC.</p>},
	issn = {0021-9606},
	doi = {10.1063/1.4901897},
	author = {Chatterjee, Prathit and Bagchi, Sayan and Sengupta, Neelanjana}
}
@article {46784,
	title = {Nanoscale interplay of membrane composition and amyloid self-assembly},
	journal = {Journal of Physical Chemistry B},
	volume = {124},
	year = {2020},
	month = {JUL},
	pages = {5837-5846},
	type = {Article},
	abstract = {<p>Cell membranes are complex assemblies of lipids and proteins exhibiting lipid compositional heterogeneity between the inner and outer leaflets of the bilayer. Aberrant protein aggregation, implicated in a number of neurodegenerative diseases including Alzheimer{\textquoteright}s, is known to result in both extracellular and intracellular deposits with divergent pathophysiological effects. Mounting evidence substantiates membrane-mediated amyloid effects and indicates membrane composition, particularly gangliosides, as a plausible factor influencing the fibrillation process. By employing exhaustive molecular dynamics simulations using a coarse-grained model, we probed the assembly behavior of amyloidogenic A beta(12-28) peptides on the chemically heterogeneous extracellular (outer) and cytosolic (inner) leaflets of a mammalian plasma membrane. Our results indicate that the compositional nature of the membrane has a crucial impact on the peptide self-assembly. Peptide oligomerization is hindered on the outer leaflet relative to the inner leaflet due to a competition between interpeptide and peptide-membrane interactions, resulting in higher population of smaller oligomers. The weaker associations among peptides on the outer membrane can be attributed to the favorable interactions of the peptides with gangliosides (GM) that characterize the extracellular membrane. At a higher peptide:GM ratio, we observe enhanced nanoclustering of GM lipids mediated by preferential GM-A beta binding. Interaction between peptide and GM further impacts local membrane curvature; there is a concomitant loss in membrane concavity due to looser GM packing. Our simulations provide molecular insights into the role of membrane composition on A beta aggregation and lend credence to earlier reports of ganglioside-mediated A beta aggregation in the outer membrane. We also demonstrate the effects of local peptide assemblies on the membrane structure and dynamics.</p>
},
	issn = {1520-6106},
	doi = {10.1021/acs.jpcb.0c03796},
	author = {Menon, Sneha and Sengupta, Neelanjana and Das, Payel}
}
