Chemistry

Effects of two solvent conditions on the free energy landscape of the BBL peripheral subunit binding domain

Document Type

Article

Abstract

BBL is a small independently folding domain with two main parallel helices. The experiment of Cα secondary shifts has shown that changing the pH from ∼7 to ∼5 results in the reduced helicity at the C-terminus of helix 2. Combining constant pH molecular dynamics with replica exchange, we sampled the protein conformation space and protonation states extensively under a neutral pH condition and an acidic condition. Our results reveal that the solvent conditions influence the free energy landscape. Under the neutral pH condition, the denatured state and the native state are well separated. The condition of the acidic pH reshapes the free energy surface, leading to a broadly populated denatured-state basin and a low free energy barrier between the denatured state and the native state. The acidic pH shifts the equilibrium between the denatured state and the native state in favor of the denatured state. Caution must be used to interpret experimental data under the acidic condition because the contribution of the denatured state is significant. Our simulation results are supported by the fact that the calculated chemical shifts are in good agreement with the experiment data. © 2011 American Chemical Society.

Publication Title

Journal of Physical Chemistry B

Publication Date

1-12-2012

Volume

116

Issue

1

First Page

646

Last Page

652

ISSN

1520-6106

DOI

10.1021/jp209791a

Keywords

conformation, free energy, nucleic acid structure, pH, solvents

Cross Post Location

Student Publications

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