Crowding alters the folding kinetics of a β-hairpin by modulating the stability of intermediates
Kurniawan, N.A. Enemark, S. Rajagopalan, R.
Kurniawan, N.A.
Enemark, S.
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Abstract
Crowded environments inside cells exert significant effects on protein structure, stability, and function, but their effects on (pre)folding dynamics and kinetics, especially at molecular levels, remain ill-understood. Here, we examine the latter for, as an initial candidate, a small de novo β-hairpin using extensive all-atom molecular dynamics simulations for crowder volume fractions φ up to 40%. We find that crowding does not introduce new folding intermediates or misfolded structures, although, as expected, it promotes compact structures and reduces the accessible conformational space. Furthermore, while hydrophobic-collapse-mediated folding is slightly enhanced, the turn-directed zipper mechanism (dominant in crowder-free situations) increases many-fold, becoming even more dominant. Interestingly, φ influences the stability of the folding intermediates (FI 1 and FI 2) in an apparently counterintuitive manner, which can be understood only by considering specific intrachain interactions and intermediate (and hierarchical) structural transitions. For φ values
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Journal of the American Chemical Society
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Date
2012-06-20
DOI
10.1021/ja302943m
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Article