Radou, G, Dreyer, FN, Tuma, R et al. (1 more author) (2014) Functional dynamics of hexameric helicase probed by hydrogen exchange and simulation. Biophysical Journal, 107 (4). 983 - 990. ISSN 0006-3495
Abstract
The biological function of large macromolecular assemblies depends on their structure and their dynamics over a broad range of timescales; for this reason, it is a significant challenge to investigate these assemblies using conventional experimental techniques. One of the most promising experimental techniques is hydrogen-deuterium exchange detected by mass spectrometry. Here, we describe to our knowledge a new computational method for quantitative interpretation of deuterium exchange kinetics and apply it to a hexameric viral helicase P4 that unwinds and translocates RNA into a virus capsid at the expense of ATP hydrolysis. Room-temperature dynamics probed by a hundred nanoseconds of all-atom molecular dynamics simulations is sufficient to predict the exchange kinetics of most sequence fragments and provide a residue-level interpretation of the low-resolution experimental results. The strategy presented here is also a valuable tool to validate experimental data, e.g., assignments, and to probe mechanisms that cannot be observed by x-ray crystallography, or that occur over timescales longer than those that can be realistically simulated, such as the opening of the hexameric ring.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 The Authors. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/3.0/). |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Mar 2015 13:32 |
Last Modified: | 17 Aug 2015 13:36 |
Published Version: | http://dx.doi.org/10.1016/j.bpj.2014.06.039 |
Status: | Published |
Publisher: | Biophysical Society |
Refereed: | Yes |
Identification Number: | 10.1016/j.bpj.2014.06.039 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:83673 |