Thermodynamics and kinetics of folding of two model peptides investigated by molecular dynamics simulations

The folding of an alpha-helix and a beta-hairpin was studied by 862 molecul ar dynamics simulations with an implicit solvation model that allowed sampl ing of a total of 4 mu s. The average effective energy is rather flat for c onformations having less than about 50% of the folded state contacts formed , except for the alpha-helix at very high temperatures. For both peptides t here is a smooth decrease of the effective energy close to the folded state . The free energy landscape shows that the helix-coil transition is not fir st order, while the beta-hairpin has one or two minima, depending on the te mperature. At low temperature (T < 1.1T(m)) there is an increase in the fol ding rate with increasing temperature as expected from an activation energy limited process. At higher temperatures the rate decreases for both peptid es which is consistent with an activation entropy dominated process. The un folding rate, by contrast, shows an Arrhenius-like behavior, i.e., it incre ases monotonously with temperature. The beta-hairpin peptide folds about 30 times slower than the alpha-helix peptide at 300 K. Multiple folding pathw ays are present for the alpha-helix, whereas the beta-hairpin initiates fol ding mainly at the beta-turn.