02367nas a2200169   4500008004100000022001400041245011700055210006900172260012500241300001100366490000800377520161600385100002402001700001802025700002502043856012902068       2014                        eng d  a0021-960600aNon-uniform early structural response of globular proteins to cold denaturing conditions: a case study with Yfh10 aNonuniform early structural response of globular proteins to col  aCIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USAbAMER INST PHYSICScNOV  a2051030 v1413 a<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 ``global'' 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>1 aChatterjee, Prathit1 aBagchi, Sayan1 aSengupta, Neelanjana  uhttps://library.ncl.res.in/content/non-uniform-early-structural-response-globular-proteins-cold-denaturing-conditions-case-0