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Statistical prediction and molecular dynamics simulation

Publication ,  Journal Article
Cooke, B; Schmidler, SC
Published in: Biophysical Journal
November 15, 2008

We describe a statistical approach to the validation and improvement of molecular dynamics simulations of macromolecules. We emphasize the use of molecular dynamics simulations to calculate thermodynamic quantities that may be compared to experimental measurements, and the use of a common set of energetic parameters across multiple distinct molecules. We briefly review relevant results from the theory of stochastic processes and discuss the monitoring of convergence to equilibrium, the obtaining of confidence intervals for summary statistics corresponding to measured quantities, and an approach to validation and improvement of simulations based on out-of-sample prediction. We apply these methods to replica exchange molecular dynamics simulations of a set of eight helical peptides under the AMBER potential using implicit solvent. We evaluate the ability of these simulations to quantitatively reproduce experimental helicity measurements obtained by circular dichroism. In addition, we introduce notions of statistical predictive estimation for force-field parameter refinement. We perform a sensitivity analysis to identify key parameters of the potential, and introduce Bayesian updating of these parameters. We demonstrate the effect of parameter updating applied to the internal dielectric constant parameter on the out-of-sample prediction accuracy as measured by cross-validation. © 2008 by the Biophysical Society.

Duke Scholars

Published In

Biophysical Journal

DOI

EISSN

1542-0086

ISSN

0006-3495

Publication Date

November 15, 2008

Volume

95

Issue

10

Start / End Page

4497 / 4511

Related Subject Headings

  • Proteins
  • Protein Folding
  • Protein Conformation
  • Models, Statistical
  • Models, Molecular
  • Models, Chemical
  • Computer Simulation
  • Biophysics
  • 51 Physical sciences
  • 34 Chemical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cooke, B., & Schmidler, S. C. (2008). Statistical prediction and molecular dynamics simulation. Biophysical Journal, 95(10), 4497–4511. https://doi.org/10.1529/biophysj.108.131623
Cooke, B., and S. C. Schmidler. “Statistical prediction and molecular dynamics simulation.” Biophysical Journal 95, no. 10 (November 15, 2008): 4497–4511. https://doi.org/10.1529/biophysj.108.131623.
Cooke B, Schmidler SC. Statistical prediction and molecular dynamics simulation. Biophysical Journal. 2008 Nov 15;95(10):4497–511.
Cooke, B., and S. C. Schmidler. “Statistical prediction and molecular dynamics simulation.” Biophysical Journal, vol. 95, no. 10, Nov. 2008, pp. 4497–511. Scopus, doi:10.1529/biophysj.108.131623.
Cooke B, Schmidler SC. Statistical prediction and molecular dynamics simulation. Biophysical Journal. 2008 Nov 15;95(10):4497–4511.
Journal cover image

Published In

Biophysical Journal

DOI

EISSN

1542-0086

ISSN

0006-3495

Publication Date

November 15, 2008

Volume

95

Issue

10

Start / End Page

4497 / 4511

Related Subject Headings

  • Proteins
  • Protein Folding
  • Protein Conformation
  • Models, Statistical
  • Models, Molecular
  • Models, Chemical
  • Computer Simulation
  • Biophysics
  • 51 Physical sciences
  • 34 Chemical sciences