Robust Automated Truncation Point Selection for Molecular Simulations

Quantities calculated from molecular simulations are often subject to an initial bias due to unrepresentative starting configurations. Initial data are usually discarded to reduce bias. Chodera's method for automated truncation point selection [J. Chem. Theory Comput. 2016, 12, 4, 1799-1805] is...

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Veröffentlicht in:Journal of chemical theory and computation Jg. 21; H. 1; S. 88
Hauptverfasser: Clark, Finlay, Cole, Daniel J, Michel, Julien
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 14.01.2025
ISSN:1549-9626, 1549-9626
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Zusammenfassung:Quantities calculated from molecular simulations are often subject to an initial bias due to unrepresentative starting configurations. Initial data are usually discarded to reduce bias. Chodera's method for automated truncation point selection [J. Chem. Theory Comput. 2016, 12, 4, 1799-1805] is popular but has not been thoroughly assessed. We reformulate White's marginal standard error rule to provide a spectrum of truncation point selection heuristics that differ in their treatment of autocorrelation. These include a method effectively equivalent to Chodera's. We test these methods on ensembles of synthetic time series modeled on free energy change estimates from long absolute binding free energy calculations. Methods that more thoroughly account for autocorrelation often show late and variable truncation times, while methods that less thoroughly account for autocorrelation often show early truncation, relative to the optimal truncation point. This increases variance and bias, respectively. We recommend a method that achieves robust performance across our test sets by balancing these two extremes. None of the methods reliably detected insufficient sampling. All heuristics tested are implemented in the open-source Python package RED (github.com/fjclark/red).
Bibliographie:ObjectType-Article-1
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ISSN:1549-9626
1549-9626
DOI:10.1021/acs.jctc.4c01359