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Exploring the conformational preferences of 20-residue peptides in isolation: Ac-Ala19-Lys + H(+)vs. Ac-Lys-Ala19 + H(+) and the current reach of DFT.

Publication ,  Journal Article
Schubert, F; Rossi, M; Baldauf, C; Pagel, K; Warnke, S; von Helden, G; Filsinger, F; Kupser, P; Meijer, G; Salwiczek, M; Koksch, B; Blum, V ...
Published in: Physical chemistry chemical physics : PCCP
March 2015

Reliable, quantitative predictions of the structure of peptides based on their amino-acid sequence information are an ongoing challenge. We here explore the energy landscapes of two unsolvated 20-residue peptides that result from a shift of the position of one amino acid in otherwise the same sequence. Our main goal is to assess the performance of current state-of-the-art density-functional theory for predicting the structure of such large and complex systems, where weak interactions such as dispersion or hydrogen bonds play a crucial role. For validation of the theoretical results, we employ experimental gas-phase ion mobility-mass spectrometry and IR spectroscopy. While unsolvated Ac-Ala19-Lys + H(+) will be shown to be a clear helix seeker, the structure space of Ac-Lys-Ala19 + H(+) is more complicated. Our first-principles structure-screening strategy using the dispersion-corrected PBE functional (PBE + vdW(TS)) identifies six distinctly different structure types competing in the low-energy regime (≈16 kJ mol(-1)). For these structure types, we analyze the influence of the PBE and the hybrid PBE0 functional coupled with either a pairwise dispersion correction (PBE + vdW(TS), PBE0 + vdW(TS)) or a many-body dispersion correction (PBE + MBD*, PBE0 + MBD*). We also take harmonic vibrational and rotational free energy into account. Including this, the PBE0 + MBD* functional predicts only one unique conformer to be present at 300 K. We show that this scenario is consistent with both experiments.

Duke Scholars

Published In

Physical chemistry chemical physics : PCCP

DOI

EISSN

1463-9084

ISSN

1463-9076

Publication Date

March 2015

Volume

17

Issue

11

Start / End Page

7373 / 7385

Related Subject Headings

  • Thermodynamics
  • Quantum Theory
  • Protein Structure, Secondary
  • Peptides
  • Models, Molecular
  • Hydrogen Bonding
  • Chemical Physics
  • 51 Physical sciences
  • 40 Engineering
  • 34 Chemical sciences
 

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Schubert, F., Rossi, M., Baldauf, C., Pagel, K., Warnke, S., von Helden, G., … Blum, V. (2015). Exploring the conformational preferences of 20-residue peptides in isolation: Ac-Ala19-Lys + H(+)vs. Ac-Lys-Ala19 + H(+) and the current reach of DFT. Physical Chemistry Chemical Physics : PCCP, 17(11), 7373–7385. https://doi.org/10.1039/c4cp05541a
Schubert, Franziska, Mariana Rossi, Carsten Baldauf, Kevin Pagel, Stephan Warnke, Gert von Helden, Frank Filsinger, et al. “Exploring the conformational preferences of 20-residue peptides in isolation: Ac-Ala19-Lys + H(+)vs. Ac-Lys-Ala19 + H(+) and the current reach of DFT.Physical Chemistry Chemical Physics : PCCP 17, no. 11 (March 2015): 7373–85. https://doi.org/10.1039/c4cp05541a.
Schubert F, Rossi M, Baldauf C, Pagel K, Warnke S, von Helden G, et al. Exploring the conformational preferences of 20-residue peptides in isolation: Ac-Ala19-Lys + H(+)vs. Ac-Lys-Ala19 + H(+) and the current reach of DFT. Physical chemistry chemical physics : PCCP. 2015 Mar;17(11):7373–85.
Schubert, Franziska, et al. “Exploring the conformational preferences of 20-residue peptides in isolation: Ac-Ala19-Lys + H(+)vs. Ac-Lys-Ala19 + H(+) and the current reach of DFT.Physical Chemistry Chemical Physics : PCCP, vol. 17, no. 11, Mar. 2015, pp. 7373–85. Epmc, doi:10.1039/c4cp05541a.
Schubert F, Rossi M, Baldauf C, Pagel K, Warnke S, von Helden G, Filsinger F, Kupser P, Meijer G, Salwiczek M, Koksch B, Scheffler M, Blum V. Exploring the conformational preferences of 20-residue peptides in isolation: Ac-Ala19-Lys + H(+)vs. Ac-Lys-Ala19 + H(+) and the current reach of DFT. Physical chemistry chemical physics : PCCP. 2015 Mar;17(11):7373–7385.
Journal cover image

Published In

Physical chemistry chemical physics : PCCP

DOI

EISSN

1463-9084

ISSN

1463-9076

Publication Date

March 2015

Volume

17

Issue

11

Start / End Page

7373 / 7385

Related Subject Headings

  • Thermodynamics
  • Quantum Theory
  • Protein Structure, Secondary
  • Peptides
  • Models, Molecular
  • Hydrogen Bonding
  • Chemical Physics
  • 51 Physical sciences
  • 40 Engineering
  • 34 Chemical sciences