title: 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.
abstract: 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.
authors.affiliation: Fritz-Haber-Institut der Max-Planck-Gesellschaft, D-14195 Berlin, Germany. schubert@fhi-berlin.mpg.de baldauf@fhi-berlin.mpg.de.
authors.forename: Franziska
authors.initials: F
authors.lastname: Schubert
authors.forename: Mariana
authors.initials: M
authors.lastname: Rossi
authors.forename: Carsten
authors.initials: C
authors.lastname: Baldauf
authors.forename: Kevin
authors.initials: K
authors.lastname: Pagel
authors.forename: Stephan
authors.initials: S
authors.lastname: Warnke
authors.forename: Gert
authors.initials: G
authors.lastname: von Helden
authors.forename: Frank
authors.initials: F
authors.lastname: Filsinger
authors.forename: Peter
authors.initials: P
authors.lastname: Kupser
authors.forename: Gerard
authors.initials: G
authors.lastname: Meijer
authors.forename: Mario
authors.initials: M
authors.lastname: Salwiczek
authors.forename: Beate
authors.initials: B
authors.lastname: Koksch
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheffler
authors.forename: Volker
authors.initials: V
authors.lastname: Blum
mesh_terms: D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D010455:Peptides