The Fip35 WW domain folds with structural and mechanistic heterogeneity in molecular dynamics simulations

Biophys J. 2009 Apr 22;96(8):L53-5. doi: 10.1016/j.bpj.2009.01.024.


We describe molecular dynamics simulations resulting in the folding the Fip35 Hpin1 WW domain. The simulations were run on a distributed set of graphics processors, which are capable of providing up to two orders of magnitude faster computation than conventional processors. Using the Folding@home distributed computing system, we generated thousands of independent trajectories in an implicit solvent model, totaling over 2.73 ms of simulations. A small number of these trajectories folded; the folding proceeded along several distinct routes and the system folded into two distinct three-stranded beta-sheet conformations, showing that the folding mechanism of this system is distinctly heterogeneous.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bayes Theorem
  • Computer Simulation*
  • Imaging, Three-Dimensional
  • Kinetics
  • Likelihood Functions
  • Models, Molecular*
  • Protein Folding*
  • Protein Stability
  • Protein Structure, Secondary
  • Protein Structure, Tertiary*
  • Solvents
  • Viscosity


  • Solvents