Solvent Mediation of Peptide Conformations: Polyproline Structures in Water, Methanol, Ethanol, and 1-Propanol as Determined by Ion Mobility Spectrometry-Mass Spectrometry

  • Tarick J. El-Baba
  • Daniel R. Fuller
  • David A. Hales
  • David H. Russell
  • David E. ClemmerEmail author
Focus: Honoring Carol V. Robinson's Election to the National Academy of Sciences: Research Article


Ion mobility spectrometry and circular dichroism spectroscopy are used to examine the populations of the small model peptide, polyproline-13 in water, methanol, ethanol, and 1-propanol over a range of solution temperatures (from 288 to 318 K). At low temperatures, the less-polar solvents (1-propanol and ethanol) favor the all-cis polyproline I helix (PPI); as the temperature is increased, the trans-configured polyproline II helix (PPII) is formed. In polar solvents (methanol and water), PPII is favored at all temperatures. From the experimental data, we determine the relative stabilities of the eight structures in methanol, ethanol, and 1-propanol, as well as four in water, all with respect to PPII. Although these conformers show relatively small differences in free energies, substantial variability is observed in the enthalpies and entropies across the structures and solvents. This requires that enthalpies and entropies be highly correlated: in 1-propanol, cis-configured PPI conformations are energetically favorable but entropically disfavored. In more polar solvents, PPI is enthalpically less favorable and entropy favors trans-configured forms. While either ΔH0 or ΔS0 can favor different structures, no conformation in any solvent is simultaneously energetically and entropically stabilized. These data present a rare opportunity to examine the origin of conformational stability.

Graphical Abstract


Ion mobility spectrometry Folding Enthalpy-entropy compensation Polyproline Structure Energetics 



T. J. E. acknowledges support from the Robert and Marjorie Mann Graduate Fellowship from Indiana University.

Funding information

This work was supported in part by funds from the Waters Corporation, the National Institutes of Health R01 GM117207-03 and R01 GM121751-01A1, and the Robert and Marjorie Mann endowment.

Supplementary material

13361_2018_2034_MOESM1_ESM.docx (83 kb)
ESM 1 (DOCX 82 kb)


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Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.Department of ChemistryIndiana UniversityBloomingtonUSA
  2. 2.Department of ChemistryHendrix CollegeConwayUSA
  3. 3.Department of ChemistryTexas A&M UniversityCollege StationUSA

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