Conformations of Unsolvated Valine-Based Peptides

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High-resolution ion mobility measurements and molecular dynamics (MD) simulations have been used to study the conformations of unsolvated valine-based peptides with up to 20 residues. In aqueous solution, valine is known to have a high propensity to form β-sheets and a low propensity to form α-helices. A variety of protonated valine-based peptides were examined in vacuo: Valn+H+, Ac-Valn-Lys+H+, Ac-Lys-Valn+H+, Valn-Gly-Gly-Valm+H+, Valn-LPro-Gly-Valm+H+, Valn-DPro-Gly-Valm+H+, Ac-Valn-Gly-Lys-Valm+H+, Ac-Valn+H+, and Arg-Valn+H+. Peptides designed to be β-hairpins were found to be random globules or helices. The β-hairpin is apparently not favored for valine-based peptides in vacuo, which is in agreement with the predictions of MD simulations. Peptides designed to be α-helices appear to be partial α/partial π-helices. Insertion of Gly-Gly, LPro-Gly, or DPro-Gly into the center of a polyvaline peptide disrupts helix formation. Some of the peptides that were expected to be random globules (because their most basic protonation site is near the N-terminus where protonation destabilizes the helix) were found to be helical with the proton located near the C-terminus. Helix formation appears to be more favorable in unsolvated valine-based peptides than in their alanine analogues. This is the reverse of what is observed in aqueous solution, but appears to parallel the helix propensities determined in polar solvents.