## Abstract

The convergence of free energy perturbation (Zwanzig's equation) and its non-equilibrium extension (Jarzynski's equation) is herein investigated from a practical point of view. We focus on cases where neither intermediate steps nor two-sided methods (Bennett, Crooks) can be used to compute the free energy difference of interest. Using model data sampled from several probability densities, as well as comparing results of actual free energy simulations with reference values, we find, in agreement with existing theoretical work, that systematic errors are strongly correlated with the variance in the distribution of energy differences / non-equilibrium work values. The bias metric Π introduced by Wu and Kofke (J. Chem. Phys. 121, 8742 (2004)) is found to be a useful test for the presence of bias, i.e. systematic error in the results. By contrast, use of the second-order cumulant approximation to approximate the full Zwanzig or Jarzynski equation leads to poorer results in almost all cases.

Original language | English |
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Pages (from-to) | 1200-1213 |

Number of pages | 14 |

Journal | Molecular Physics: an international journal in the field of chemical physics |

Volume | 115 |

Issue number | 9-12 |

DOIs | |

Publication status | Published - 2017 |

## Austrian Fields of Science 2012

- 103006 Chemical physics

## Keywords

- Free energy perturbation
- Zwanzig's equation
- Jarzynski's equation
- cumulant expansion
- QM/MM free energy simulation
- indirect cycle
- MOLECULAR SIMULATION
- NONEQUILIBRIUM MEASUREMENTS
- THERMODYNAMIC INTEGRATION
- FORCE-FIELD
- EQUILIBRIUM
- SYSTEMS
- MECHANICS
- ACCURACY
- EQUALITY
- SAMPLE