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Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin

[Image: see text] 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...

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Autores principales: Pressé, Steve, Peterson, Jack, Lee, Julian, Elms, Phillip, MacCallum, Justin L., Marqusee, Susan, Bustamante, Carlos, Dill, Ken
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064692/
https://www.ncbi.nlm.nih.gov/pubmed/24898871
http://dx.doi.org/10.1021/jp500611f
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author Pressé, Steve
Peterson, Jack
Lee, Julian
Elms, Phillip
MacCallum, Justin L.
Marqusee, Susan
Bustamante, Carlos
Dill, Ken
author_facet Pressé, Steve
Peterson, Jack
Lee, Julian
Elms, Phillip
MacCallum, Justin L.
Marqusee, Susan
Bustamante, Carlos
Dill, Ken
author_sort Pressé, Steve
collection PubMed
description [Image: see text] 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.
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spelling pubmed-40646922015-05-22 Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin Pressé, Steve Peterson, Jack Lee, Julian Elms, Phillip MacCallum, Justin L. Marqusee, Susan Bustamante, Carlos Dill, Ken J Phys Chem B [Image: see text] 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. American Chemical Society 2014-05-22 2014-06-19 /pmc/articles/PMC4064692/ /pubmed/24898871 http://dx.doi.org/10.1021/jp500611f Text en Copyright © 2014 American Chemical Society Open Access on 05/22/2015
spellingShingle Pressé, Steve
Peterson, Jack
Lee, Julian
Elms, Phillip
MacCallum, Justin L.
Marqusee, Susan
Bustamante, Carlos
Dill, Ken
Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin
title Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin
title_full Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin
title_fullStr Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin
title_full_unstemmed Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin
title_short Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin
title_sort single molecule conformational memory extraction: p5ab rna hairpin
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064692/
https://www.ncbi.nlm.nih.gov/pubmed/24898871
http://dx.doi.org/10.1021/jp500611f
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