Title
Single molecule conformational memory extraction: P5ab RNA hairpin
Date Issued
19 June 2014
Access level
open access
Resource Type
journal article
Author(s)
Pressé S.
Peterson J.
Lee J.
Elms P.
Maccallum J.L.
Marqusee S.
Dill K.
University of California
Publisher(s)
American Chemical Society
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. © 2014 American Chemical Society.
Start page
6597
End page
6603
Volume
118
Issue
24
Language
English
OCDE Knowledge area
Física atómica, molecular y química
Bioquímica, Biología molecular
Scopus EID
2-s2.0-84902951610
PubMed ID
Source
Journal of Physical Chemistry B
ISSN of the container
15206106
Sponsor(s)
National Institutes of Health GM32543
National Stroke Foundation
National Institute of General Medical Sciences R01GM034993 NIGMS
Sources of information:
Directorio de Producción Científica
Scopus