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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
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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. |
format | Online Article Text |
id | pubmed-4064692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
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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