Skinner, SP, Radou, G, Tuma, R orcid.org/0000-0003-0047-0013 et al. (2 more authors) (2019) Estimating Constraints for Protection Factors from HDX-MS Data. Cell Press, 116 (7). pp. 1194-1203. ISSN 0006-3495
Abstract
Hydrogen/deuterium exchange monitored by mass spectrometry is a promising technique for rapidly fingerprinting structural and dynamical properties of proteins. The time-dependent change in the mass of any fragment of the polypeptide chain depends uniquely on the rate of exchange of its amide hydrogens, but determining the latter from the former is generally not possible. Here, we show that, if time-resolved measurements are available for a number of overlapping peptides that cover the whole sequence, rate constants for each amide hydrogen exchange (or equivalently, their protection factors) may be extracted and the uniqueness of the solutions obtained depending on the degree of peptide overlap. However, in most cases, the solution is not unique, and multiple alternatives must be considered. We provide a statistical method that clusters the solutions to further reduce their number. Such analysis always provides meaningful constraints on protection factors and can be used in situations in which obtaining more refined experimental data is impractical. It also provides a systematic way to improve data collection strategies to obtain unambiguous information at single-residue level (e.g., for assessing protein structure predictions at atomistic level).
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Biophysical Society. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). |
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: | 03 Apr 2019 11:42 |
Last Modified: | 22 May 2019 15:06 |
Status: | Published |
Publisher: | Biophysical Society |
Identification Number: | 10.1016/j.bpj.2019.02.024 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:144392 |