The energy landscape of unsolvated peptides: the role of context in the stability of alanine/glycine helices.
Ion mobility measurements have been used to examine the conformations present for unsolvated Ac-(AG)(7)A+H(+) and (AG)(7)A+H(+) peptides (Ac = acetyl, A = alanine, and G = glycine) over a broad temperature range (100-410 K). The results are compared to those recently reported for Ac-A(4)G(7)A(4)+H(+) and A(4)G(7)A(4)+H(+), which have the same compositions but different sequences. Ac-(AG)(7)A+H(+) shows less conformational diversity than Ac-A(4)G(7)A(4)+H(+); it is much less helical than Ac-A(4)G(7)A(4)+H(+) at the upper end of the temperature range studied, and at low temperatures, one of the two Ac-A(4)G(7)A(4)+H(+) features assigned to helical conformations is missing for Ac-(AG)(7)A+H(+). Molecular dynamics simulations suggest that the different conformational preferences are not due to differences in the stabilities of the helical states, but differences in the nonhelical states: it appears that Ac-(AG)(7)A+H(+) is more flexible and able to adopt lower energy globular conformations (compact random looking three-dimensional structures) than Ac-A(4)G(7)A(4)+H(+). The helix to globule transition that occurs for Ac-(AG)(7)A+H(+) at around 250-350 K is not a direct (two-state) process, but a creeping transition that takes place through at least one and probably several intermediates.
Hartings
Matthew R
MR
Chemistry Department, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405-7102, USA.
Kinnear
Brian S
BS
Jarrold
Martin F
MF
D000409:Alanine / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D010455:Peptides; D000409:Alanine; D005998:Glycine