Conformations of unsolvated valine-based peptides

High-resolution ion mobility measurements and molecular dynamics (MD) simul ations have been used to study the conformations of unsolvated valine-based peptides with up to 20 residues: In aqueous solution, valine is known to h ave a high propensity to form beta-sheets and a low propensity to form alph a-helices. A variety of protonated valine-based peptides were examined in v acuo: 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 a pparently not favored for valine-based peptides in vacuo, which is in agree ment 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 disrupt s helix formation. Some of the peptides that were expected to be random glo bules (because their most basic protonation site is near the N-terminus whe re protonation destabilizes the:helix) were found to be helical with the pr oton located near the C-terminus. Helix formation appears to be more favora ble in unsolvated valine-based peptides than in their alanine analogues. Th is is the reverse of what is observed in aqueous solution, but appears to p arallel the helix propensities determined in polar solvents.