Comparison of the effects of 2,2,2-trifluoroethanol on peptide and protein structure and function

Toward a common aggregation mechanism for a β-barrel protein family: Insights derived from a stable dimeric species

“…However, at relatively high concentrations, TFE also penetrates the hydrophobic core of the proteins disrupting the internal core stability thus initiating unfolding. This is in direct contrast to the observed effects on peptidic structures whereby TFE interacts weakly with non-polar side chain groups and does not disrupt hydrophobic interactions between peptide side chains [8]. At around 30 % v/v TFE, alcohol molecules associate so as to minimize their contact with water, resulting in the formation of micelle-like clusters with the hydrophobic groups located inside.…”

“…However, this co-solvent has also the ability to alter the native structure of proteins [7]. In this sense, the consequences of adding TFE upon secondary structural elements within a protein is distinct from that observed with a standalone discrete peptide [8]. TFE does not operate like classical denaturants such as urea, but it shows a dual concentration-dependent effect.…”

Structure of hen egg-white lysozyme solvated in TFE/water: a molecular dynamics simulation study based on NMR data

“…So this conformational ensemble offers the best representation of the TFE state of HEWL. A comparison of calculated with measured (Buck et al 1993) values of observables accessible by spectroscopic techniques such as far-UV CD or fluorescence spectroscopy for HEWL (Buck et al 1993;Povey et al 2007;D'Amico et al 2011) or its constituting peptides (Yang et al 1995;Povey et al 2007) would not be very conclusive for the following reasons: (i) CD spectra only indicate overall helical content, not which helices are present or not; (ii) fluorescence data only reflect modifications in the relative positions of the six Trp side chains of HEWL, but not the details with respect to the individual Trp residues; (iii) our MD simulations were done in 70 % TFE in order to match the conditions of the NMR experiment , whereas the CD and fluorescence measurements were done at 15 % (Buck et al Table 1 (a) (b) (c) (d) Fig. 8 Final configurations of two MD simulations aligned and colored according to the positional root-mean-square deviaton of the C a atoms.…”

“…Hen egg white lysozyme (HEWL) is one of the proteins whose conformation has been studied extensively in TFE solutions (Buck et al 1993(Buck et al , 1996Yang et al 1995;Hoshino et al 1997;Povey et al 2007). Low concentrations of added TFE co-solvent (\10 % (v/v)) stabilise the native structure of the protein (Buck et al 1993; O (v/v) b Energy-minimised X-ray structure 1AKI (Artymiuk et al 1982) c Final configuration of simulation ''MD_pH2_TFE'' d T is increased from 310 to 400 K over 11.4 ns, then decreased to 310 K over the next 6.0 ns and then kept at 310 K for 2.6 ns e See Table 2 f Configuration after 11.4 ns of simulation MD_pH2_TFE_HT g T is decreased from 400 to 310 K over 2 ns and then kept at 310 K for 18 ns Fig.…”

“…1 The different, sequential HEWL simulations. All initial coordinates have been generated from one of the two PDB files with PDB entry code 1AKI (Artymiuk et al 1982) or 1E8L (Schwalbe et al 2001 (Buck et al 1993Povey et al 2007;D'Amico et al 2011). Studies by SAXS show that the protein has an increased radius of gyration relative to the native state, although it is still relatively compact (Hoshino et al 1997).…”