Influence of charge and size of terminal amino‐acid residues on local conformational states and shape of alanine‐based peptides

Makowska, Joanna; Bagiñska, Katarzyna; Skwierawska, Agnieszka; Liwo, Adam; Chmurzyński, Lech; Scheraga, Harold A.

doi:10.1002/bip.21077

Cited by 19 publications

(35 citation statements)

References 42 publications

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“…The results of this study, along with those of our previous work 27,28,36 support the hypothesis that the presence of likecharged residues at the ends of a chain reversal can stabilize its structure. It should be noted that, even though this hypothesis might sound counterintuitive, it is supported by the fact that polylysine chains form α-helical structures at low pH; 51 in these structures, lysine side chains point outside to shield the backbone from solvent.…”

Section: Discussionsupporting

confidence: 90%

Thermodynamics of the Protonation Equilibria of Two Fragments of N-Terminal β-Hairpin of FPB28 WW Domain

2011

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The pK(a) values of two peptides derived from the formin-binding protein 28 WW domain [Ac-Lys-Thr-Ala-Asp-Gly-Lys-Thr-NH(2) (D7), Ac-Tyr-Lys-Thr-Ala-Asp-Gly-Lys-Thr-Tyr-NH(2) (D9)] were determined by potentiometric titration in the temperature range from 25 to 60 °C, and their heat capacities were determined, by differential scanning calorimetry, in the temperature range from 10 to 90 °C. For both peptides, heat capacity has a maximum at t ≈ 50 °C, with height about 0.1 kcal/(mol × deg), suggesting that a modest unfolding transition occurs. The first two pK(a)'s are low at temperatures below 50 °C, suggesting that the two lysine residues are close to each other and the peptides have bent shapes at lower temperatures; this effect is greater for D7 compared with D9. With increasing temperature beyond 50 °C (i.e., that of the thermodynamic unfolding transition), pK(a1) and pK(a2) increase rapidly for D9, whereas their temperature variation is less significant for D7. This observation, and the fact that the enthalpies and entropies of the dissociation of the two first protons (determined from the temperature dependence of the respective pK(a)'s) decrease significantly near the transition temperature, suggest that the peptide undergoes a transition from a bent to an amorphous shape and that the presence of charged lysine residues stabilizes the folded state.

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Section: Discussionsupporting

confidence: 90%

Thermodynamics of the Protonation Equilibria of Two Fragments of N-Terminal β-Hairpin of FPB28 WW Domain

2011

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“…All peptides under study were synthesized by using the procedure described in our earlier work [11]. The purities of the peptides were 99.98 and 99.99 % for D7 and D9 M, respectively, as assessed by analytical HPLC and MALDI-TOF analyses.…”

Section: Peptide Synthesismentioning

confidence: 99%

“…This is an independently forming region whose folding is not induced by a b-hairpin and is consequently an excellent object by which to study the factors that influence b-hairpin formation. Results from our preliminary conformational studies of two original fragments of the N-terminal part of the FBP28 protein (1E0L: 12-18 D7 and the 1E0L: [11][12][13][14][15][16][17][18][19]; the D9 M is a point mutation of the sequence) [9] fragments suggest that these peptides do not form stable three-dimensional structures in solution (water). However, it was found that D7 forms a large fraction of bent conformations.…”

Section: Introductionmentioning

confidence: 99%

Investigations of copper(II) complexation by fragments of the FBP28 protein using isothermal titration (ITC) and differential scanning calorimetry (DSC)

Makowska

Wyrzykowski

Hirniak

et al. 2015

J Therm Anal Calorim

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Isothermal titration calorimetry (ITC) was used to study the interactions between copper(II) ions and peptides with sequences taken from the N-terminal loop of the FBP28 protein (formin-binding protein) WW domain: AcLys-Thr-Ala-Asp-Gly-Lys-Thr-NH 2 (D7) and Ac-Tyr-LysThr-Ala-Asn-Gly-Lys-Thr-Tyr-NH 2 (D9 M), respectively. Measurements were taken at 298.15 K in 20 mM 2-(Nmorpholino)ethanesulfonic acid buffer solution at a pH of 6. The stoichiometry, conditional stability constants and thermodynamic parameters (D ITC G, D ITC H and D ITC S) for the pertinent complexation reactions were determined. Furthermore, the thermal stability of peptide conformations in the presence and absence of copper(II) in the system was investigated using differential scanning calorimetry. Finally, a general procedure on how to include the effect of buffer competition with the peptide for the metal as well as proton competition with the metal for the peptide and the buffer's component during ITC data analysis is described.

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“…9−14 The unfolded peptide backbone clearly has conformation preferences that are sequence and context dependent. 15−20 Thus, defining the conformations of peptides in unfolded states has become a problem of current interest and importance. Advances in this effort will enable construction of more accurate models of intrinsically disordered proteins, enable elucidation of fundamental principles of protein folding, and potentially help design novel functional peptide modulators of biological processes.…”

Section: Introductionmentioning

confidence: 99%

Peptide Conformation Analysis Using an Integrated Bayesian Approach

Xiao

Kallenbach

Zhang

2014

J. Chem. Theory Comput.

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Unlike native proteins that are amenable to structural analysis at atomic resolution, unfolded proteins occupy a manifold of dynamically interconverting structures. Defining the conformations of unfolded proteins is of significant interest and importance, for folding studies and for understanding the properties of intrinsically disordered proteins. Short chain protein fragments, i.e., oligopeptides, provide an excellent test-bed in efforts to define the conformational ensemble of unfolded chains. Oligomers of alanine in particular have been extensively studied as minimalist models of the intrinsic conformational preferences of the peptide backbone. Even short alanine peptides occupy an ensemble of substates that are distinguished by small free energy differences, so that the problem of quantifying the conformational preferences of the backbone remains a fundamental challenge in protein biophysics. Here, we demonstrate an integrated computational-experimental-Bayesian approach to quantify the conformational ensembles of the model trialanine peptide in water. In this approach, peptide conformational substates are first determined objectively by clustering molecular dynamics snapshots based on both structural and dynamic information. Next, a set of spectroscopic data for each conformational substate is computed. Finally, a Bayesian statistical analysis of both experimentally measured spectroscopic data and computational results is carried out to provide a current best estimate of the substate population ensemble together with corresponding confidence intervals. This distribution of substates can be further systematically refined with additional high-quality experimental data and more accurate computational modeling. Using an experimental data set of NMR coupling constants, we have also applied this approach to characterize the conformation ensemble of trivaline in water.

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Influence of charge and size of terminal amino‐acid residues on local conformational states and shape of alanine‐based peptides

Cited by 19 publications

References 42 publications

Thermodynamics of the Protonation Equilibria of Two Fragments of N-Terminal β-Hairpin of FPB28 WW Domain

Thermodynamics of the Protonation Equilibria of Two Fragments of N-Terminal β-Hairpin of FPB28 WW Domain

Investigations of copper(II) complexation by fragments of the FBP28 protein using isothermal titration (ITC) and differential scanning calorimetry (DSC)

Peptide Conformation Analysis Using an Integrated Bayesian Approach

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