@article {109406,
	title = {New Insights into the Folding of a β-​Sheet Miniprotein in a Reduced Space of Collective Hydrogen Bond Variables: Application to a Hydrodynamic Analysis of the Folding Flow},
	journal = {J. Phys. Chem. B},
	volume = {117},
	year = {2013},
	pages = {6092-6105},
	abstract = {A new anal. of the 20 μs equil. folding​/unfolding mol. dynamics simulations of the three-​stranded antiparallel β-​sheet miniprotein (beta3s) in implicit solvent is presented.  The conformation space is reduced in dimensionality by introduction of linear combinations of hydrogen bond distances as the collective variables making use of a specially adapted principal component anal. (PCA)​; i.e., to make structured conformations more pronounced, only the formed bonds are included in detg. the principal components.  A three-​dimensional (3D) subspace gives a meaningful representation of the folding behavior.  The first component, to which eight native hydrogen bonds make the major contribution (four in each beta hairpin)​, is found to play the role of the reaction coordinate for the overall folding process, while the second and third components distinguish the structured conformations.  The representative points of the trajectory in the 3D space are grouped into conformational clusters that correspond to locally stable conformations of beta3s identified in earlier work.  A simplified kinetic network based on the three components is constructed, and it is complemented by a hydrodynamic anal.  The latter, making use of passive tracers in 3D space, indicates that the folding flow is much more complex than suggested by the kinetic network.  A 2D representation of streamlines shows there are vortexes which correspond to repeated local rearrangement, not only around min. of the free energy surface but also in flat regions between min.  The vortexes revealed by the hydrodynamic anal. are apparently not evident in folding pathways generated by transition-​path sampling.  Making use of the fact that the values of the collective hydrogen bond variables are linearly related to the Cartesian coordinate space, the RMSD between clusters is detd.  The transition rates show an approx. exponential correlation with distance in the hydrogen bond subspace.  Comparison with the many published studies shows good agreement with the present anal. for the parts that can be compared, supporting the robust character of the authors{\textquoteright} understanding of this hydrogen atom of protein folding.},
	author = {Igor V. Kalgin and Amedeo Caflisch and Sergei F. Chekmarev and Martin Karplus}
}
