Dataset Information

Bayesian Uncertainty Quantification for Bond Energies and Mobilities Using Path Integral Analysis.

ABSTRACT: Dynamic single-molecule force spectroscopy is often used to distort bonds. The resulting responses, in the form of rupture forces, work applied, and trajectories of displacements, are used to reconstruct bond potentials. Such approaches often rely on simple parameterizations of one-dimensional bond potentials, assumptions on equilibrium starting states, and/or large amounts of trajectory data. Parametric approaches typically fail at inferring complicated bond potentials with multiple minima, while piecewise estimation may not guarantee smooth results with the appropriate behavior at large distances. Existing techniques, particularly those based on work theorems, also do not address spatial variations in the diffusivity that may arise from spatially inhomogeneous coupling to other degrees of freedom in the macromolecule. To address these challenges, we develop a comprehensive empirical Bayesian approach that incorporates data and regularization terms directly into a path integral. All experimental and statistical parameters in our method are estimated directly from the data. Upon testing our method on simulated data, our regularized approach requires less data and allows simultaneous inference of both complex bond potentials and diffusivity profiles. Crucially, we show that the accuracy of the reconstructed bond potential is sensitive to the spatially varying diffusivity and accurate reconstruction can be expected only when both are simultaneously inferred. Moreover, after providing a means for self-consistently choosing regularization parameters from data, we derive posterior probability distributions, allowing for uncertainty quantification.

SUBMITTER: Chang JC

PROVIDER: S-EPMC4564684 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Publications

Bayesian Uncertainty Quantification for Bond Energies and Mobilities Using Path Integral Analysis.

Chang Joshua C JC Fok Pak-Wing PW Chou Tom T

Biophysical journal 20150901 5

Dynamic single-molecule force spectroscopy is often used to distort bonds. The resulting responses, in the form of rupture forces, work applied, and trajectories of displacements, are used to reconstruct bond potentials. Such approaches often rely on simple parameterizations of one-dimensional bond potentials, assumptions on equilibrium starting states, and/or large amounts of trajectory data. Parametric approaches typically fail at inferring complicated bond potentials with multiple minima, whi ...[more]

PMID: 26331254

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Dataset Information

Bayesian Uncertainty Quantification for Bond Energies and Mobilities Using Path Integral Analysis.

Publications

Bayesian Uncertainty Quantification for Bond Energies and Mobilities Using Path Integral Analysis.

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