Mechanism by which 2,2,2-trifluoroethanol/water mixtures stabilize secondary-structure formation in peptides: a molecular dynamics study.
Molecular dynamics simulation techniques have been used to investigate the effect of 2,2,2-trifluoroethanol (TFE) as a cosolvent on the stability of three different secondary structure-forming peptides: the alpha-helix from Melittin, the three-stranded beta-sheet peptide Betanova, and the beta-hairpin 41-56 from the B1 domain of protein G. The peptides were studied in pure water and 30% (vol/vol) TFE/water mixtures at 300 K. The simulations suggest that the stabilizing effect of TFE is induced by the preferential aggregation of TFE molecules around the peptides. This coating displaces water, thereby removing alternative hydrogen-bonding partners and providing a low dielectric environment that favors the formation of intrapeptide hydrogen bonds. Because TFE interacts only weakly with nonpolar residues, hydrophobic interactions within the peptides are not disrupted. As a consequence, TFE promotes stability rather than inducing denaturation.
Dipartimento di Chimica, Ingegneria Chimica e Materiali Università Degli Studi, Via Vetoio, 67010 L'Aquila, Italy. roccata@caspur.it
Danilo
D
Roccatano
Giorgio
G
Colombo
Marco
M
Fioroni
Alan E
AE
Mark
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D055592:Biophysical Phenomena; D001703:Biophysics; D004355:Drug Stability; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D008555:Melitten / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry; D012997:Solvents; D013816:Thermodynamics; D014270:Trifluoroethanol; D014867:Water
D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D010455:Peptides; D011506:Proteins; D012997:Solvents; C113273:betanova protein, synthetic; D014867:Water; D008555:Melitten; D014270:Trifluoroethanol