Intrinsic Propensities of Amino Acid Residues in GxG Peptides Inferred from Amide I′ Band Profiles and NMR Scalar Coupling Constants

Hagarman, Andrew; Measey, Thomas J.; Mathieu, Daniel; Schwalbe, Harald; Schweitzer‐Stenner, Reinhard

doi:10.1021/ja9058052

Cited by 125 publications

(356 citation statements)

References 96 publications

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“…Different kinds of vibrational spectroscopy have been used in combination to analyze the mixed spectra that result when bands from individual backbone conformers are not resolved but instead are superimposed (20,21). Hopefully this type of analysis can be tested in future work by comparison with the dipeptide results reported here.…”

Section: Estimation Of Errors and Comparison With Literature Resultsmentioning

confidence: 99%

Populations of the three major backbone conformations in 19 amino acid dipeptides

Grdadolnik

Mohaček-Grošev

Baldwin

et al. 2011

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

104

199

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The amide III region of the peptide infrared and Raman spectra has been used to determine the relative populations of the three major backbone conformations (P II , β, and α R ) in 19 amino acid dipeptides. The results provide a benchmark for force field or other methods of predicting backbone conformations in flexible peptides. There are three resolvable backbone bands in the amide III region. The major population is either P II or β for all dipeptides except Gly, whereas the α R population is measurable but always minor (≤10%) for 18 dipeptides. (The Gly φ,ψ map is complex and so is the interpretation of the amide III bands of Gly.) There are substantial differences in the relative β and P II populations among the 19 dipeptides. The band frequencies have been assigned as P II , 1,317-1,306 cm −1 ; α R , 1,304-1,294 cm −1 ; and β, 1,294-1,270 cm −1 . The three bands were measured by both attenuated total reflection spectroscopy and by Raman spectroscopy. Consistent results, both for band frequency and relative population, were obtained by both spectroscopic methods. The β and P II bands were assigned from the dependence of the 3 JðH N ,H α Þ coupling constant (known for all 19 dipeptides) on the relative β population. The P II band assignment agrees with one made earlier from Raman optical activity data. The temperature dependences of the relative β and P II populations fit the standard model with Boltzmann-weighted energies for alanine and leucine between 30 and 60°C.vibrational spectroscopy | backbone conformations | spectral populations | aqueous solution A basic unsolved problem in protein folding is making accurate calculations of the folding energetics of flexible peptides. Accurate experimental results for the major backbone conformations are needed to test prediction methods. Even the simple problem of calculating the φ,ψ map of the alanine dipeptide is beyond the reach of standard force fields used in molecular dynamics simulations (1). There are two probable reasons: one is that the energy differences between the major backbone conformations are small, and the second is that standard force fields contain so many parameters that errors cannot be found readily by comparing simulations with experimental results. The ability to calculate accurately the relative energies of the various backbone conformations is needed for simulating early stages of the protein folding process, which is an important current problem in molecular biophysics.When simulated by standard force fields, the φ,ψ map of the alanine dipeptide has three major conformational basins, P II , β, and α R . Different force fields agree on this point but give widely varying results for the populations in the three basins (1). The φ,ψ maps of the 19 amino acid residues (Pro excluded) from the protein structure database show the same three basins and are similar in outline for the various residues if data for Gly and Pre-Pro are excluded in addition to Pro (2). The three basins are centered approximately at P II (−75°, 145°), β (−120°, 120°), a...

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Section: Estimation Of Errors and Comparison With Literature Resultsmentioning

confidence: 99%

Populations of the three major backbone conformations in 19 amino acid dipeptides

Grdadolnik

Mohaček-Grošev

Baldwin

et al. 2011

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

104

199

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“…Interestingly, studies of the alanine dipeptide in vacuo are conclusive in discarding the right-handed α-helix (αR) or the polyproline II (PII) conformations as low energy minima. This is an intriguing result since the former is often found in helical parts of globular proteins [19] and the latter is known to be the most abundant structure found in solution [20]. This result suggests that the environment created by either the rest of the protein or the solvent substantially modifies the conformational profile of the molecule.…”

Section: Introductionmentioning

confidence: 92%

Effect of the solvent on the conformational behavior of the alanine dipeptide deduced from MD simulations

Rubio-Martínez

Tomás

Pérez

2017

Journal of Molecular Graphics and Modelling

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Graphical abstract Highlights The manuscript describes a computational study of the differential conformational behavior of the alanine dipeptide in diverse solvents including chloroform, methanol, DMSO, water and methyl formamide.  This study is important to understand the conformational behavior of peptides in diverse solvents, since the dialanine dipeptide is a model molecule to for peptides.  The manuscript discusses the role of inter-and intra-molecular interactions to understand the differential behavior of the molecule in the diverse solvents.2  This work aims to shed light into the controversy found in the literature between experimental and theoretical calculations of the dialanine dipeptide in water.  There has never been published a comparative computational study of the effect of the solvent on the molecule. AbstractIn general, peptides do not exhibit a well-defined conformational profile in solution. However, despite the experimental blurred picture associated with their structure, compelling spectroscopic evidence shows that peptides exhibit local order. The conformational profile of a peptide is the result of a balance between intramolecular interactions between different atoms of the molecule and intermolecular interactions between atoms of the molecule and the solvent. Accordingly, the conformational profile of a peptide will change upon the properties of the solvent it is soaked. To get insight into the balance between intra-and intermolecular interactions on the conformational preferences of the peptide backbone we have studied the conformational profile of the alanine dipeptide in diverse solvents using molecular dynamics as sampling technique. Solvents

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“…Results from a recent structural analysis of a more limited set of GxG peptides (x = A, V, L, E, F, S, M, K), which quantitatively explored the entire conformational ensemble of the respective x residue, seem to point into the same direction, revealing only a very limited sampling of regions associated with helical, b-turn (excluding serine) and g-turn conformations. [6] However, this study did not include the above-mentioned turn-promoting residues, namely D, N, T, and C. MD simulations mostly suggest a statistical coillike distribution of nearly all amino acid residues in unfolded peptides (with the exception of P), and thus imply that they can sample the entire sterically allowed region of the Ramachandran plot. [22] Moreover, this study did not indicate any turn propensities for specific amino acids.…”

Section: Introductionmentioning

confidence: 96%

“…[3] This is the case for alanine, for which recent spectroscopic studies have convincingly shown an exceptionally high propensity to adopt poly-A C H T U N G T R E N N U N G proline II (PPII)-like conformations. [4][5][6] Other amino acid residues with predominantly aliphatic or aromatic side chains (e.g., L, K, V, F, M) exhibit a more balanced distribution of conformational sampling in the upper-left quadrant of the Ramachandran plot, which encompasses PPII and different types of b-strand-like structures. [7,8] The propensity for helical structures is rather low for all of these residues, which, particularly for alanine, is at variance with predictions from molecular dynamics (MD) simulations using a variety of different force fields.…”

Section: Introductionmentioning

confidence: 99%

Amino Acids with Hydrogen‐Bonding Side Chains have an Intrinsic Tendency to Sample Various Turn Conformations in Aqueous Solution

Hagarman

Mathieu

Toal

et al. 2011

Chemistry A European J

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160

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Local structure in unfolded proteins, especially turn segments, has been suggested to initiate the hierarchical protein-folding process. To determine the intrinsic propensity to form such turn structures, amide I' band profiles of the Raman, IR, and vibrational circular dichroism (VCD) spectra, and several structure-sensitive NMR J-coupling constants, have been measured for a series of GxG (x=D, N, T, C) peptides, in which the central x residues are abundant in various turn motifs in folded proteins. In addition, we revisited earlier measured GSG experimental data. To check whether this relatively high propensity for these residues to sample turns reflects an intrinsic propensity, the experimental data were analyzed in terms of conformational distributions that can be described as a superposition of two-dimensional Gaussian distributions associated with different so-called mesostates. The analysis reveals that the investigated residues sample dihedral angles similar to those found in the corner residues of various turns, namely, type I/I', II/II', and IV β-turns. Aspartic acid (D) was found to predominantly sample regions attributed to turns, including distributions at the upper border of the upper-right quadrant of the Ramachandran plot, which bear some resemblance to asx-turns observed in proteins. This conformation enables hydrogen bonding between the side-chain carboxylate and the C-terminal amide group. Altogether, the study shows that the high propensity for T, S, C, N, and D to be located in turn motifs reflects, to a substantial degree, an intrinsic property and supports the role of these residues as initiation sites for hierarchical folding processes that can lead to compact structures in the unfolded state of peptides and proteins.

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Intrinsic Propensities of Amino Acid Residues in GxG Peptides Inferred from Amide I′ Band Profiles and NMR Scalar Coupling Constants

Cited by 125 publications

References 96 publications

Populations of the three major backbone conformations in 19 amino acid dipeptides

Populations of the three major backbone conformations in 19 amino acid dipeptides

Effect of the solvent on the conformational behavior of the alanine dipeptide deduced from MD simulations

Amino Acids with Hydrogen‐Bonding Side Chains have an Intrinsic Tendency to Sample Various Turn Conformations in Aqueous Solution

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