Single molecule conformational memory extraction: P5ab RNA hairpin

Steve Presse, Jack Peterson, Julian Lee, Phillip Elms, Justin L. Maccallum, Susan Marqusee, Carlos Bustamante, Ken Dill

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Extracting kinetic models from single molecule data is an important route to mechanistic insight in biophysics, chemistry, and biology. Data collected from force spectroscopy can probe discrete hops of a single molecule between different conformational states. Model extraction from such data is a challenging inverse problem because single molecule data are noisy and rich in structure. Standard modeling methods normally assume (i) a prespecified number of discrete states and (ii) that transitions between states are Markovian. The data set is then fit to this predetermined model to find a handful of rates describing the transitions between states. We show that it is unnecessary to assume either (i) or (ii) and focus our analysis on the zipping/unzipping transitions of an RNA hairpin. The key is in starting with a very broad class of non-Markov models in order to let the data guide us toward the best model from this very broad class. Our method suggests that there exists a folding intermediate for the P5ab RNA hairpin whose zipping/unzipping is monitored by force spectroscopy experiments. This intermediate would not have been resolved if a Markov model had been assumed from the onset. We compare the merits of our method with those of others.

Original languageEnglish (US)
Pages (from-to)6597-6603
Number of pages7
JournalJournal of Physical Chemistry B
Volume118
Issue number24
DOIs
StatePublished - Jun 19 2014
Externally publishedYes

Fingerprint

RNA
Data storage equipment
Molecules
Spectrum Analysis
Biophysics
molecules
Humulus
Spectroscopy
biophysics
Inverse problems
biology
folding
spectroscopy
routes
chemistry
Kinetics
probes
kinetics
Experiments

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Presse, S., Peterson, J., Lee, J., Elms, P., Maccallum, J. L., Marqusee, S., ... Dill, K. (2014). Single molecule conformational memory extraction: P5ab RNA hairpin. Journal of Physical Chemistry B, 118(24), 6597-6603. https://doi.org/10.1021/jp500611f

Single molecule conformational memory extraction : P5ab RNA hairpin. / Presse, Steve; Peterson, Jack; Lee, Julian; Elms, Phillip; Maccallum, Justin L.; Marqusee, Susan; Bustamante, Carlos; Dill, Ken.

In: Journal of Physical Chemistry B, Vol. 118, No. 24, 19.06.2014, p. 6597-6603.

Research output: Contribution to journalArticle

Presse, S, Peterson, J, Lee, J, Elms, P, Maccallum, JL, Marqusee, S, Bustamante, C & Dill, K 2014, 'Single molecule conformational memory extraction: P5ab RNA hairpin', Journal of Physical Chemistry B, vol. 118, no. 24, pp. 6597-6603. https://doi.org/10.1021/jp500611f
Presse S, Peterson J, Lee J, Elms P, Maccallum JL, Marqusee S et al. Single molecule conformational memory extraction: P5ab RNA hairpin. Journal of Physical Chemistry B. 2014 Jun 19;118(24):6597-6603. https://doi.org/10.1021/jp500611f
Presse, Steve ; Peterson, Jack ; Lee, Julian ; Elms, Phillip ; Maccallum, Justin L. ; Marqusee, Susan ; Bustamante, Carlos ; Dill, Ken. / Single molecule conformational memory extraction : P5ab RNA hairpin. In: Journal of Physical Chemistry B. 2014 ; Vol. 118, No. 24. pp. 6597-6603.
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