Energy landscape of the trpzip2 peptide.

  • Hugh Nymeyer
  • Published 2009 in The journal of physical chemistry. B


Replica exchange simulations are used to study the energy landscape of trpzip2, a model beta-hairpin system, using the AMBER99sb force field and explicit solvent. The total simulation time is 300 ns per replica (approximately 10 mus total). The trp side chains are observed to adopt multiple packing arrangements with a freezing temperature below 273 K in the simulated system. The secondary structure and native hydrogen bonds melt out cooperatively around 273 K. The residual beta-strand structure and antiparallel bonding persist at high temperature. These results provide a model for the three apparent melting transitions observed experimentally in this system. The dominant folding mechanism of trpzip2 in this model appears to be zipping, which is consistent with recent measurements on similar hairpins. Structures for which the turn is native-like and the termini are non-native-like collectively form a metastable intermediate. Most of the stabilizing enthalpy is gained after the formation of the turn. Equilibrium thermodynamic quantities are compared against experiment. Although the AMBER99sb force field reproduces the native structure with good fidelity, the stability of the native state is significantly underpredicted with a melting temperature near 273 K, and the relative heat capacity is only about one tenth of its experimental value.

DOI: 10.1021/jp806749b

Cite this paper

@article{Nymeyer2009EnergyLO, title={Energy landscape of the trpzip2 peptide.}, author={Hugh Nymeyer}, journal={The journal of physical chemistry. B}, year={2009}, volume={113 24}, pages={8288-95} }