Two different regimes in alcohol-induced coil–helix transition: effects of 2,2,2-trifluoroethanol on proteins being either independent of or enhanced by solvent structural fluctuations

Ohgi, Hiroyo; Imamura, Hiroshi; Sumi, Tetsuya; Nishikawa, Keiko; Koga, Yoshikata; Westh, Peter; Morita, Takeshi

doi:10.1039/d0cp05103a

Cited by 6 publications

(13 citation statements)

References 67 publications

(152 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, at 7 M of [TFE],

Δ Γ_{23}

for TFE was ~10, which is comparable with the absolute value of

Δ Γ_{23}

for urea (Figure S1a,b), even though the absolute m ‐value for urea is more than six times larger than that for TFE. Such enhancement of helix‐induction coupled with the large concentration fluctuations of the cosolvent (>2 M) is unique for TFE, and has been discussed in our previous study (Ohgi et al, 2021). This could be predicted based on the molecular origin of TFE‐induced helix formation, that is,

Δ Γ_{23}

, depicted at lower concentrations of TFE.…”

Section: Resultssupporting

confidence: 63%

“…the Boltzmann constant, and T is the temperature) and a 33 is provided using the bulk KB integrals as follows (Ohgi et al, 2021;Pierce et al, 2008):…”

Section: Preferential Binding and Effects Of Cosolvents On Protein St...mentioning

confidence: 99%

“…PBP for the two-stranded helices of GCN4-p1, Γ h 23 , and that for two isolated coils, Γ c 23 , can be given by Kirkwood-Buff (KB) integrals G α ij as (Ohgi et al, 2021;Pierce et al, 2008)…”

Section: Preferential Binding and Effects Of Cosolvents On Protein St...mentioning

confidence: 99%

“…PBP for the two‐stranded helices of GCN4‐p1,

Γ_{23}^{normalh}

, and that for two isolated coils,

Γ_{23}^{normalc}

, can be given by Kirkwood–Buff (KB) integrals

G_{italicij}^{α}

as (Ohgi et al, 2021; Pierce et al, 2008)

Γ_{23}^{α} = ρ_{3} (G_{23}^{α} - G_{21}^{α}), (α = h or c),

where

ρ_{3}

is the number density of the cosolvent. The KB integrals are defined by

G_{italicij} = \int_{0}^{\infty} [g_{italicij} (r) - 1] 4 π r^{2} dr,

where

g_{italicij} (r)

is a radial distribution function between components i and j .…”

Section: Background Of Theoretical Analysismentioning

confidence: 99%

“…Utilizing those KB integrals,

a_{33}

was calculated from Equation () as a function of [TFE]. We found that,

a_{33}

was nearly equal to 1 at concentrations less than ~2 M, that is, mole fraction of TFE being approximately 0.04 (Ohgi et al, 2021). Thus, the concentration dependence of

Δ G_{helix}

depends only on

Δ Γ_{23}

at the low concentrations of TFE (see Equations and ).…”

Section: Background Of Theoretical Analysismentioning

confidence: 99%

See 4 more Smart Citations

Molecular mechanism of the common and opposing cosolvent effects of fluorinated alcohol and urea on a coiled coil protein

Nakata,

Okamoto,

Sumi

et al. 2023

Protein Science

Self Cite

View full text Add to dashboard Cite

Alcohols and urea are widely used as effective protein denaturants. Among monohydric alcohols, 2,2,2‐trifluoroethanol (TFE) has large co‐solvent effects as a helix stabilizer in proteins. In contrast, urea efficiently denatures ordered native structures, including helices, into coils. These opposing co‐solvent effects of TFE and urea are well known, even though both preferentially bind to proteins; however, the underlying molecular mechanism remains controversial. Co‐solvent‐dependent relative stability between native and denatured states is rigorously related to the difference in preferential binding parameters (PBPs) between these states. In this study, GCN4‐p1 with two‐stranded coiled coil helices was employed as a model protein, and molecular dynamics simulations for the helix dimer and isolated coil were conducted in aqueous solutions with 2 M TFE and urea. As 2 M co‐solvent aqueous solutions did not exhibit clustering of co‐solvent molecules, we were able to directly investigate the molecular origin of the excess PBP without considering the enhancement effect of PBPs arising from the concentration fluctuations. The calculated excess PBPs of TFE for the helices and those of urea for the coils were consistent with experimentally observed stabilization of helix by TFE and that of coil by urea. The former was caused by electrostatic interactions between TFE and side chains of the helices, while the latter was attributed to both electrostatic and dispersion interactions between urea and the main chains. Unexpectedly, reverse‐micelle‐like orientations of TFE molecules strengthened the electrostatic interactions between TFE and the side chains, resulting in strengthening of TFE solvation.This article is protected by copyright. All rights reserved.

show abstract

“…For instance, at 7 M of [TFE],

Δ Γ_{23}

for TFE was ~10, which is comparable with the absolute value of

Δ Γ_{23}

Δ Γ_{23}

, depicted at lower concentrations of TFE.…”

Section: Resultssupporting

confidence: 63%

“…the Boltzmann constant, and T is the temperature) and a 33 is provided using the bulk KB integrals as follows (Ohgi et al, 2021;Pierce et al, 2008):…”

Section: Preferential Binding and Effects Of Cosolvents On Protein St...mentioning

confidence: 99%

Section: Preferential Binding and Effects Of Cosolvents On Protein St...mentioning

confidence: 99%

“…PBP for the two‐stranded helices of GCN4‐p1,

Γ_{23}^{normalh}

, and that for two isolated coils,

Γ_{23}^{normalc}

, can be given by Kirkwood–Buff (KB) integrals

G_{italicij}^{α}

as (Ohgi et al, 2021; Pierce et al, 2008)

Γ_{23}^{α} = ρ_{3} (G_{23}^{α} - G_{21}^{α}), (α = h or c),

where

ρ_{3}

is the number density of the cosolvent. The KB integrals are defined by

G_{italicij} = \int_{0}^{\infty} [g_{italicij} (r) - 1] 4 π r^{2} dr,

where

g_{italicij} (r)

is a radial distribution function between components i and j .…”

Section: Background Of Theoretical Analysismentioning

confidence: 99%

“…Utilizing those KB integrals,

a_{33}

was calculated from Equation () as a function of [TFE]. We found that,

a_{33}

was nearly equal to 1 at concentrations less than ~2 M, that is, mole fraction of TFE being approximately 0.04 (Ohgi et al, 2021). Thus, the concentration dependence of