The energy landscape of unsolvated peptides: helix formation and cold denaturation in Ac-A4G7A4 + H+.
Ion mobility measurements and molecular dynamics simulations were performed for unsolvated A4G7A4 + H+ and Ac-A4G7A4 + H+ (Ac = acetyl, A = alanine, G = glycine) peptides. As expected, A4G7A4 + H+ adopts a globular conformation (a compact, random-looking, three-dimensional structure) over the entire temperature range examined (100-410 K). Ac-A4G7A4 + H+ on the other hand is designed to have a flat energy landscape with a marginally stable helical state. This peptide shows at least four different conformations at low temperatures (<230 K). The two conformations with the largest cross sections are attributed to - and partial -helices, while the one with the smallest cross section is globular. The other main conformation may be partially helical. Ac-A4G7A4 + H+ becomes predominantly globular at intermediate temperatures and then becomes more helical as the temperature is raised further. This unexpected behavior may be due to the helix having a higher vibrational entropy than the globular state, as predicted by some recent calculations (Ma, B.; Tsai, C.-J.; Nussinov, R. Biophys. J. 2000, 79, 2739-2753).
Kinnear
Brian S
BS
Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA.
Hartings
Matthew R
MR
Jarrold
Martin F
MF
D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D003080:Cold Temperature; D003198:Computer Simulation; D005998:Glycine / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D010455:Peptides; D000409:Alanine; D005998:Glycine