Conformations of unsolvated valine-based peptides

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 beta-sheets and a low propensity to form alpha-helices. A variety of protonated valine-based peptides were examined in vacuo: Val(n)+H+, Ac-Val(n)-Lys+H+, Ac-Lys-Val(n)+H+, Val(n)-Gly-Gly-Val(m)+H+, Val(n)-(L)Pro-Gly-Val(m)+H+, Val(n)-(D)Pro-Gly-Val(m)+H+, Ac-Val(n)-Gly-Lys-Val(m)+H+, Ac-Val(n)+H+, and Arg-Val(n)+H+. Peptides designed to be P-hairpins were found to be random globules or helices. The beta-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 alpha-helices appear to be partial alpha/partial pi-helices. Insertion of Gly-Gly, (L)Pro-Gly, or (D)Pro-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.