Additive Transfer Free Energies of the Peptide Backbone Unit That Are Independent of the Model Compound and the Choice of Concentration Scale

Matthew T Auton, D. Wayne Bolen

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

With knowledge of individual transfer free energies of chemical groups that become newly exposed on protein denaturation and assuming the group transfer free energy contributions are additive, it should be possible to predict the stability of a protein in the presence of denaturant. Unfortunately, several unresolved issues have seriously hampered quantitative development of this transfer model for protein folding/unfolding. These issues include the lack of adequate demonstration that group transfer free energies (ΔG tr) are additive and independent of the choice of model compound, the problem arising from dependence of ΔGtr on concentration scales, the lack of knowledge of activity coefficients, and the validity of the mathematical constructs used in obtaining ΔGtr values. Regarding transfer from water to 1 M concentrations of the naturally occurring osmolytes, trimethylamine-N-oxide (TMAO), sarcosine, betaine, proline, glycerol, sorbitol, sucrose, trehalose, and urea, using cyclic glycylglycine, zwitterionic glycine peptides, and N-acetylglycine amide peptides as models for the peptide backbone of proteins, we set out to address these issues and obtain ΔGtr values for the peptide backbone unit. We demonstrate experimental approaches that obviate the choice of concentration scale and demonstrate additivity in ΔGtr of the peptide backbone unit for all solvent systems studied. Evidence is presented to show that the ΔGtr values are independent of the chemical model studied, and experimental conditions are given to illustrate when the mathematical constructs are valid and when activity coefficients can be ignored. Resolution of the long-standing issues that have stymied development of the transfer model now make it possible to design transfer experiments that yield reliable and quantitative values for the interactions between osmolyte-containing solvents and native and unfolded protein.

Original languageEnglish (US)
Pages (from-to)1329-1342
Number of pages14
JournalBiochemistry
Volume43
Issue number5
DOIs
StatePublished - Feb 10 2004
Externally publishedYes

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Energy Transfer
Free energy
Peptides
Protein Unfolding
Activity coefficients
Proteins
Glycylglycine
Sarcosine
Chemical Models
Protein Denaturation
Protein folding
Trehalose
Denaturation
Sorbitol
Protein Stability
Protein Folding
Amides
Glycerol
Glycine
Sucrose

ASJC Scopus subject areas

  • Biochemistry

Cite this

Additive Transfer Free Energies of the Peptide Backbone Unit That Are Independent of the Model Compound and the Choice of Concentration Scale. / Auton, Matthew T; Bolen, D. Wayne.

In: Biochemistry, Vol. 43, No. 5, 10.02.2004, p. 1329-1342.

Research output: Contribution to journalArticle

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