Identification of simple reaction coordinates from complex dynamics

J Chem Phys. 2017 Jan 28;146(4):044109. doi: 10.1063/1.4974306.


Reaction coordinates are widely used throughout chemical physics to model and understand complex chemical transformations. We introduce a definition of the natural reaction coordinate, suitable for condensed phase and biomolecular systems, as a maximally predictive one-dimensional projection. We then show that this criterion is uniquely satisfied by a dominant eigenfunction of an integral operator associated with the ensemble dynamics. We present a new sparse estimator for these eigenfunctions which can search through a large candidate pool of structural order parameters and build simple, interpretable approximations that employ only a small number of these order parameters. Example applications with a small molecule's rotational dynamics and simulations of protein conformational change and folding show that this approach can filter through statistical noise to identify simple reaction coordinates from complex dynamics.

Publication types

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

MeSH terms

  • Animals
  • Biphenyl Compounds / chemistry*
  • Cattle
  • Molecular Dynamics Simulation*
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Small Molecule Libraries / chemistry*
  • Trypsin / metabolism


  • Biphenyl Compounds
  • Protease Inhibitors
  • Small Molecule Libraries
  • Trypsin