Role of aromatic residues in stabilizing the secondary and tertiary structure of avian pancreatic polypeptide

Palermo, Nicholas Y.; Csontos, József; Murphy, Richard F.; Lovas, Sándor

doi:10.1002/qua.21521

Cited by 15 publications

(24 citation statements)

References 22 publications

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“…This functional was chosen because it reliable reproduces high level ab initio results for weakly polar interactions in polypeptides and systems in which dispersion plays an important role 10, 12, 14, 15. The Boys and Bernardi method was used to correct the basis set superposition error (BSSE) 43…”

Section: Methodsmentioning

confidence: 99%

Molecular Dynamics Analysis of the Conformations of a β-Hairpin Miniprotein

2010

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Molecular Dynamics simulations of a β-hairpin miniprotein, CLN025, were performed to examine the conformational stability of the peptide in H 2 O at 278 K, 300 K, 333 K and 363 K as well as in TFE, MeOH and DMSO at 300 K. CLN025 is a variant of the Chignolin miniprotein, in which the terminal Gly residues of Chignolin are replaced with Tyr residues, which leads to a 29.7 K increase in melting temperature. The energy of the intramolecular interactions were calculated using DFT quantum chemical calculations at the BH and HLYP/cc-pVTZ level of theory. CLN025 maintained a β-hairpin conformation in all environments. The β-hairpin is stabilized by hydrogen bonds, an electrostatic interaction between the charged termini of the peptide and weakly polar interactions. The interaction between the backbones of the N and C-terminal strands accounts for −97.32 to −120.87 kcal mol −1 of the stabilization energy. The energy of the CH-π interactions between Tyr2 and Pro4 were between −1.80 and −8.9 kcal mol −1 and the energy of the Tyr2-Trp9 Ar-Ar interaction was between −0.43 and −8.11 kcal mol −1 . Increasing temperature caused the Tyr2-Pro4 CH-π and the Tyr2-Trp9 and Tyr2-Tyr10 Ar-Ar interactions to become less favorable but the Tyr1-Trp9 interaction became more favorable and played an important role in stabilizing the β-hairpin of CLN025 that resulted in the increased melting temperature. The weakly polar interactions play an important role in the structure and stability of CLN025 and other proteins.

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Section: Methodsmentioning

confidence: 99%

Molecular Dynamics Analysis of the Conformations of a β-Hairpin Miniprotein

2010

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“…Weakly polar interactions can be as strong as hydrogen bonds. 5–12 They play an important role in the stabilization of secondary structure such as α-helices, 5 and the tertiary structure of peptides such as the TC5b 8 and APP 10, 12 miniproteins. Numerous β-hairpins have been designed to take advantage the aromatic-aromatic (Ar-Ar) interactions, 13–17 cation-π interactions, 16–18 and CH-π interactions.…”

Section: Introductionmentioning

confidence: 99%

VCD spectroscopic properties of the β‐hairpin forming miniprotein CLN025 in various solvents

2010

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Electronic and vibrational circular dichroism are often used to determine the secondary structure of proteins, because each secondary structure has a unique spectrum. In order to determine these spectral features, polypeptides that are known to adopt a particular conformation along their entire length are studied ideally. Little is known about the vibrational circular dichroic spectroscopic features of the β-hairpin. In this study, the VCD spectral features of a decapeptide, YYDPETGTWY (CLN025), which forms a stable β-hairpin that is stabilized by intramolecular weakly polar interactions and hydrogen bonds were determined. Molecular Dynamics simulations and ECD spectropolarimetry were used to confirm that CLN025 adopts a β-hairpin in water, TFE, MeOH and DMSO and to examine differences in the secondary structure, hydrogen bonds and weakly polar interactions. CLN025 was synthesized by microwave-assisted solid phase peptide synthesis with Nα-Fmoc protected amino acids. The VCD spectra displayed a (−,+,−) pattern with bands at 1640 to 1656 cm−1, 1667 to 1687 cm−1 and 1679 to 1686 cm−1 formed by the overlap of a lower frequency negative couplet and a higher frequency positive couplet. A maximum IR absorbance was observed at 1647 to 1663 cm−1 with component bands at 1630 cm−1, 1646 cm−1, 1658 cm−1 and 1675 to 1680 cm−1 that are indicative of the β-sheet, random meander, either random meander or loop and turn, respectively. These results are similar to the results of others, who examined the VCD spectra of β-hairpins formed by DPro-Xxx turns and indicate that observed pattern is typical of β-hairpins.

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“…Weakly polar interactions in the hydrophobic core of aPP include the CH-interactions of Tyr7 with Pro8 and Phe20, Phe20 with Pro5, Pro8 and Leu24, Tyr21 with Gln25, and Tyr27 with Pro2, Gln4, Pro5 and Val31, an Ar-NH interaction between Tyr7 and Gly9 and an Ar-Ar interaction between Tyr7 and Phe20. It was, thus, possible to show that the total stabilization energy of these interactions, recently determined here, is Ϫ27.33 kcal mol Ϫ1 [19]. …”

Section: Introductionmentioning

confidence: 95%

“…This functional was chosen because it closely approximates high-level results for weakly polar interactions and dispersion systems [19,[21][22][23][24]. The BHandHLYP functional is expressed as follows:…”

Section: Interaction Energy Calculationsmentioning

confidence: 99%

Evaluation of methods to cap molecular fragments in calculating energies of interaction in avian pancreatic polypeptide

Hatfield

Palermo

Csontos

et al. 2007

Int J of Quantum Chemistry

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The accuracy of the determination of the energy of interaction between Phe20 and the Pro5-Thr6-Tyr7-Pro8 complex inside the hydrophobic core of avian pancreatic polypeptide was investigated using three capping strategies for molecular fractionation with conjugated caps and DFT quantum chemical calculations at the BHandHLYP/cc-pVTZ level of theory. The most accurate determination resulted from acetylation of the alpha-amino group combined with methyl amidation of the alpha-carbonyl group with relative deviations less than 10%. Combinations of hydrogenation of the alpha-amino group with the replacement of the alpha-carbonyl group with a hydrogen and the hydrogenation of the alpha-amino group with methylation of the alpha-carbonyl group were less accurate, leading to relative deviations up to 35%. Choice of capping methods depends on the structural features of the polypeptide system, the desired accuracy and the available computational resources.

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Role of aromatic residues in stabilizing the secondary and tertiary structure of avian pancreatic polypeptide

Cited by 15 publications

References 22 publications

Molecular Dynamics Analysis of the Conformations of a β-Hairpin Miniprotein

Molecular Dynamics Analysis of the Conformations of a β-Hairpin Miniprotein

VCD spectroscopic properties of the β‐hairpin forming miniprotein CLN025 in various solvents

Evaluation of methods to cap molecular fragments in calculating energies of interaction in avian pancreatic polypeptide

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