Integrating molecular dynamics simulations with chemical probing experiments using SHAPE-FIT

Serdal Kirmizialtin, Scott P. Hennelly, Alexander Schug, Jose N. Onuchic, Karissa Y. Sanbonmatsu

Research output: Contribution to journalArticle

Abstract

Integration and calibration of molecular dynamics simulations with experimental data remain a challenging endeavor. We have developed a novel method to integrate chemical probing experiments with molecular simulations of RNA molecules by using a native structure-based model. Selective 2′-hydroxyl acylation by primer extension (SHAPE) characterizes the mobility of each residue in the RNA. Our method, SHAPE-FIT, automatically optimizes the potential parameters of the force field according to measured reactivities from SHAPE. The optimized parameter set allows simulations of dynamics highly consistent with SHAPE probing experiments. Such atomistic simulations, thoroughly grounded in experiment, can open a new window on RNA structure-function relations.

Original languageEnglish (US)
Pages (from-to)215-234
Number of pages20
JournalMethods in Enzymology
Volume553
DOIs
StatePublished - Jan 1 2015

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Acylation
Molecular Dynamics Simulation
Hydroxyl Radical
Molecular dynamics
Computer simulation
RNA
Experiments
Calibration
Molecules

Keywords

  • Modeling
  • Molecular dynamics simulation
  • Riboswitch
  • RNA
  • SHAPE

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Integrating molecular dynamics simulations with chemical probing experiments using SHAPE-FIT. / Kirmizialtin, Serdal; Hennelly, Scott P.; Schug, Alexander; Onuchic, Jose N.; Sanbonmatsu, Karissa Y.

In: Methods in Enzymology, Vol. 553, 01.01.2015, p. 215-234.

Research output: Contribution to journalArticle

Kirmizialtin, Serdal ; Hennelly, Scott P. ; Schug, Alexander ; Onuchic, Jose N. ; Sanbonmatsu, Karissa Y. / Integrating molecular dynamics simulations with chemical probing experiments using SHAPE-FIT. In: Methods in Enzymology. 2015 ; Vol. 553. pp. 215-234.
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