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Ensembles Are Required to Handle Aleatoric and Parametric Uncertainty in Molecular Dynamics Simulation
Maxime Vassaux1, Shunzhou Wan1, Wouter Edeling2
1Centre for Computational Science, Department of Chemistry, University College London, London WC1H 0AJ, United Kingdom.
Journal of Chemical Theory and Computation
|July 19, 2021
Summary
Uncertainty in molecular dynamics simulations stems from input parameters and random seeds. Robust analysis requires ensemble averaging over random seeds for reliable results.
Area of Science:
- Computational physics and chemistry
- Biomolecular simulations
- Materials science
Background:
- Classical molecular dynamics is widely used but lacks reproducibility.
- This is partly due to insufficient uncertainty quantification (UQ).
Purpose of the Study:
- To systematically analyze uncertainty sources in molecular dynamics simulations.
- To investigate the impact of input parameters and random seeds on simulation output.
- To assess UQ for binding free energy calculations.
Main Methods:
- Performed a systematic UQ analysis on the NAMD code.
- Replaced fixed input parameters with random variables.
- Conducted a sensitivity analysis to identify dominant parameters.
- Ensemble-averaged simulations over random seeds.
Main Results:
- Uncertainty arises from input parameters and random seeds.
- Six out of 175 parameters significantly influence simulation output variance.
- Ensemble averaging over random seeds reduces uncertainty in binding free energy calculations.
- Without ensemble averaging, predicted free energy uncertainty increases fivefold.
Conclusions:
- Input parameters and random seeds are critical sources of uncertainty.
- Ensemble averaging over random seeds is essential for robust UQ in molecular dynamics.
- Accurate uncertainty quantification is crucial for reliable molecular dynamics simulations.
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