@article{bibcite_254,
  keywords = {Kinetics, Peptides, Protein Denaturation, Protein Folding, Thermodynamics, Protein Conformation, Fluorescence Resonance Energy Transfer, Molecular Dynamics Simulation},
  author = {P. Schuetz and R. Wuttke and B. Schuler and A. Caflisch},
  title = {Free energy surfaces from single-distance information},
  abstract = {<p>We propose a network-based method for determining basins and barriers of complex free energy surfaces (e.g., the protein folding landscape) from the time series of a single intramolecular distance. First, a network of transitions is constructed by clustering the points of the time series according to the short-time distribution of the signal. The transition network, which reflects the short-time kinetics, is then used for the iterative determination of individual basins by the minimum-cut-based free energy profile, a barrier-preserving one-dimensional projection of the free energy surface. The method is tested using the time series of a single C(\&beta;)-C(\&beta;) distance extracted from equilibrium molecular dynamics (MD) simulations of a structured peptide (20 residue three-stranded antiparallel \&beta;-sheet). Although the information of only one distance is employed to describe a system with 645 degrees of freedom, both the native state and the unfolding barrier of about 10 kJ/mol are determined with remarkable accuracy. Moreover, non-native conformers are identified by comparing long-time distributions of the same distance. To examine the applicability to single-molecule F\&ouml;rster resonance energy transfer (FRET) experiments, a time series of donor and acceptor photons is generated using the MD trajectory. The native state of the \&beta;-sheet peptide is determined accurately from the emulated FRET signal. Applied to real single-molecule FRET measurements on a monomeric variant of \&lambda;-repressor, the network-based method correctly identifies the folded and unfolded populations, which are clearly separated in the minimum-cut-based free energy profile.</p>},
  year = {2010},
  journal = {The Journal of Physical Chemistry B},
  volume = {114},
  pages = {15227-15235},
  month = {2010 Nov 25},
  issn = {1520-5207},
  doi = {10.1021/jp1053698},
  language = {eng},
}