A direct comparison of helix propensity in proteins and peptides

Myers, Jeffrey K.; Pace, C. Nick; Scholtz, J. Martin

doi:10.1073/pnas.94.7.2833

Cited by 125 publications

(138 citation statements)

References 45 publications

Supporting

Mentioning

123

Contrasting

Order By: Relevance

“…Therefore, it seems likely that solvation differences play an important role in determining both the rank order and magnitude of helix propensities in 40% TFE. A similar conclusion was reached in comparing the two peptide systems in water (Myers et al, 1997a(Myers et al, , 1997b. Our comparison of propensity scales in water revealed that reasonable qualitative agreement exists between propensities measured in various systems (Myers et al, 1997a(Myers et al, , 1997b.…”

Section: Discussionsupporting

confidence: 82%

“…A similar conclusion was reached in comparing the two peptide systems in water (Myers et al, 1997a(Myers et al, , 1997b. Our comparison of propensity scales in water revealed that reasonable qualitative agreement exists between propensities measured in various systems (Myers et al, 1997a(Myers et al, , 1997b. This allowed an experimentally based consensus scale of helix propensities to be derived (Pace & Scholtz, 1997).…”

Section: Discussionsupporting

confidence: 73%

See 1 more Smart Citation

Trifluoroethanol effects on helix propensity and electrostatic interactions in the helical peptide from ribonuclease T₁

1998

Self Cite

View full text Add to dashboard Cite

Trifluoroethanol (TFE) is often used to increase the helicity of peptides to make them usable as models of helices in proteins. We have measured helix propensities for all 20 amino acids in water and two concentrations of trifluoroethanol, 15 and 40% (v/v) using, as a model system, a peptide derived from the sequence of the a-helix of ribonuclease T I . There are three main conclusions from our studies. (1) TFE alters electrostatic interactions in the ribonuclease T I helical peptide such that the dependence of the helical content on pH is lost in 40% TFE. (2) Helix propensities measured in 15% TFE correlate well with propensities measured in water, however, the correlation with propensities measured in 40% TFE is significantly worse. (3) Propensities measured in alanine-based peptides and the ribonuclease T I peptide in TFE show very poor agreement, revealing that TFE greatly increases the effect of sequence context. Keywords: a-helix; helical propensity; peptide; ribonuclease TI ; TFE; trifluoroethanol The tendency of some short peptides to form helical structure in solution has led to their use as models for protein folding and stability. These include synthetic peptides of de novo design (some recent reviews: Chakrabartty & Baldwin, 1995; Scholtz & Baldwin, 1995;Kallenbach et al., 1996), and protein fragments (e.g., Goodman & Kim, 1989;Waltho et al., 1993;Myers et al., 1996). Structured peptides can serve as models for investigating the contribution of local interactions to protein folding and stability (Muiioz & Serrano, 1996;Myers et al., 1996).2,2,2-TrifluoroethanoI (TFE) is a co-solvent that has been shown to stabilize helical structure in peptides (Goodman et al., 1963;Nelson & Kallenbach, 1986;Jasanoff & Fersht, 1994; CammersGoodwin et al., 1996; Luo & Baldwin, 1997 and references therein). Peptide fragments of protein helices often show little helix formation in water, and TFE is frequently used to induce helix formation (Sonnischen et al., 1992;Hamada et al., 1995;Kemmink & Creighton, 1995;Yang et al., 1995;Bolin et al., 1996). Although its use is widespread, the mechanism of TFE stabilization of secondary structure is not clear. One important question is whether helix propensities of the amino acids measured in water still apply in aqueous TFE solutions. This question has been addressed recently in alanine-based peptides by Baldwin and co-workers (Rohl et al., 1996;Luo & Baldwin, 1997). For reasons that are not completely clear, in water the helix propensities are twice as large in alaninebased peptides than in peptides based on natural protein sequences. Because TFE is used so widely, it is important to compare its effect on helix formation in natural peptide sequences.Recently, we have developed a variant of the small protein ribonuclease TI (RNase T I ) and a peptide corresponding to the single a-helix of RNase T I as a model system. We have used the T I peptide/protein system previously to compare directly helix propensities in peptides and proteins (Myers et al., 1997a(Myers et al., , 1...

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 73%

Trifluoroethanol effects on helix propensity and electrostatic interactions in the helical peptide from ribonuclease T₁

1998

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

“…k, which represents the minimum number of helical residues required to produce the CD signal, is an empirically determined constant that ranges from 3 to 4.3 (23,24). We adopted the value of 3 (23). [ ] helix , which represents the mean residue ellipticity of a complete helix, is given by Ϫ42,500(1Ϫ 3͞N r ) (23).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Exploring atomistic details of pH-dependent peptide folding

Khandogin

Chen

Brooks

2006

Proc. Natl. Acad. Sci. U.S.A.

101

View full text Add to dashboard Cite

Modeling pH-coupled conformational dynamics allows one to probe many important pH-dependent biological processes, ranging from ATP synthesis, enzyme catalysis, and membrane fusion to protein folding͞misfolding and amyloid formation. This work illustrates the strengths and capabilities of continuous constant pH molecular dynamics in exploring pH-dependent conformational transitions in proteins by revisiting an experimentally well studied model protein fragment, the C peptide from ribonuclease A. The simulation data reveal a bell-shaped pH profile for the total helix content, in agreement with experiment, and several pairs of electrostatic interactions that control the relative populations of unfolded and partially folded states of various helical lengths. The latter information greatly complements and extends that attainable by current experimental techniques. The present work paves the way for new and exciting applications, such as the study of pH-dependent molecular mechanism in the formation of amyloid comprising peptides from Alzheimer's and Parkinson's diseases.C peptide ͉ conformational equilibrium ͉ helix formation ͉ molecular dynamics ͉ RNAse A M any important biological phenomena, including ATP synthesis, enzyme catalysis, membrane fusion, protein folding͞misfolding and aggregation involve pH-dependent conformational dynamics. To enable the exploration of these processes through computer simulation, a continuous constant pH molecular dynamics (CPHMD) method has been developed to effect a direct coupling between protonation and conformational dynamics in a macroscopic continuum solvent (1, 2). The CPHMD method introduces a direct coupling of solution pH conditions into molecular dynamics simulations, whereby the protonation states of protein ionizable side chains are not fixed but fluctuate in response to pH and the polypeptides local conformational state. It can be applied not only to the firstprinciples prediction of protein pKa values, which we have demonstrated in recent work (3), but also to the exploration of pH-coupled protein folding processes, an area where the traditional simulation methods employing preassigned fixed protonation states may break down (4). Here, we illustrate the utility of CPHMD simulations in studying pH-dependent peptide folding of the experimentally well characterized model peptide from the N terminus of ribonuclease A, the C peptide (5-8). A main objective of the paper is to demonstrate that CPHMD simulations can quantify the pH-modulated conformational populations and reveal direct correlations between electrostatic interactions and the pH-induced helix-coil transitions. Using a peptide with abundant experimental data, we show that the atomistic details arising from our simulation study not only complement but also extend the information attainable by current experimental techniques.The 13-residue N-terminal fragment from ribonuclease A, commonly known as the C peptide, is the shortest amino acid sequence that displays pH-dependent partial ␣-helix formation in water. Exten...

show abstract

The relative order of helical propensity of amino acids changes with solvent environment

Krittanai

Johnson

2000

Proteins

View full text Add to dashboard Cite

A model peptide of sequence Ac-Y-VAXAK-VAXAK-VAXAK-NH(2), where X is substituted with one of nineteen amino acids (P excluded), was synthesized and titrated with methanol to study helical propensity as a function of solvent environment. The CD spectra of these peptides are largely random coil in 2 mM sodium phosphate buffer (pH 5.5) and show a conformational change to alpha-helix with increasing methanol content. Singular value decomposition was used to correct the CD spectra for the absorbing side chains of W, Y, F, C, and M, and this correction can be substantial. With correction both W and F become good helix formers. The free energy for helix propagation was calculated using the Lifson-Roig statistical model for each of the nineteen amino acids at each point in their titration. The results show that the rank order of helical propensity for the nineteen amino acids changes with solvent environment. This result will be particularly important if proteins undergo hydrophobic collapse before secondary structures are formed, because amino acids can then see different solvent environments as the secondary structures are formed. Related amino acids are found to have interesting correlations in the shape of their titration curves. This finding provides one explanation for the limiting 70% accuracy in predicting secondary structure from sequence, since the helical propensities used are calculated for an average solvent environment. Proteins 2000;39:132-141.

show abstract

A direct comparison of helix propensity in proteins and peptides

Cited by 125 publications

References 45 publications

Trifluoroethanol effects on helix propensity and electrostatic interactions in the helical peptide from ribonuclease T₁

Trifluoroethanol effects on helix propensity and electrostatic interactions in the helical peptide from ribonuclease T₁

Exploring atomistic details of pH-dependent peptide folding

The relative order of helical propensity of amino acids changes with solvent environment

Contact Info

Product

Resources

About

A direct comparison of helix propensity in proteins and peptides

Cited by 125 publications

References 45 publications

Trifluoroethanol effects on helix propensity and electrostatic interactions in the helical peptide from ribonuclease T1

Trifluoroethanol effects on helix propensity and electrostatic interactions in the helical peptide from ribonuclease T1

Exploring atomistic details of pH-dependent peptide folding

The relative order of helical propensity of amino acids changes with solvent environment

Contact Info

Product

Resources

About

Trifluoroethanol effects on helix propensity and electrostatic interactions in the helical peptide from ribonuclease T₁

Trifluoroethanol effects on helix propensity and electrostatic interactions in the helical peptide from ribonuclease T₁