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dc.contributor.author
Hajnic, Matea
dc.contributor.author
Osorio Iregui, Juan
dc.contributor.author
Žagrović, Bojan
dc.date.accessioned
2019-04-04T11:38:48Z
dc.date.available
2017-06-11T14:12:01Z
dc.date.available
2019-04-04T11:38:48Z
dc.date.issued
2014-12-01
dc.identifier.issn
1362-4962
dc.identifier.issn
0305-1048
dc.identifier.issn
1362-4954
dc.identifier.other
10.1093/nar/gku1035
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/93432
dc.identifier.doi
10.3929/ethz-b-000093432
dc.description.abstract
Many critical processes in the cell involve direct binding between RNAs and proteins, making it imperative to fully understand the physicochemical principles behind such interactions at the atomistic level. Here, we use molecular dynamics simulations and 15 μs of sampling to study the behavior of amino acids and amino acid sidechain analogs in high-concentration aqueous solutions of standard RNA nucleobases. Structural and energetic analysis of simulated systems allows us to derive interaction propensity scales for different amino acid/nucleobase combinations. The derived scales closely match and greatly extend the available experimental data, providing a comprehensive foundation for studying RNA–protein interactions in different contexts. By using these scales, we demonstrate a statistically significant connection between nucleobase composition of human mRNA coding sequences and nucleobase interaction propensities of their cognate protein sequences. For example, pyrimidine density profiles of mRNAs match uracil-propensity profiles of their cognate proteins with a median Pearson correlation coefficient of R = −0.70. Our results provide support for the recently proposed hypotheses that mRNAs and their cognate proteins may be physicochemically complementary to each other and bind, especially if unstructured, with the complementarity level being negatively influenced by mRNA adenine content. Finally, we utilize the derived scales to refine the complementarity hypothesis and closely examine its physicochemical underpinnings.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Oxford University Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Computational analysis of amino acids and their sidechain analogs in crowded solutions of RNA nucleobases with implications for the mRNA–protein complementarity hypothesis
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2014-10-31
ethz.journal.title
Nucleic Acids Research
ethz.journal.volume
42
en_US
ethz.journal.issue
21
en_US
ethz.journal.abbreviated
Nucleic Acids Res.
ethz.pages.start
12984
en_US
ethz.pages.end
12994
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.nebis
000038633
ethz.publication.place
Oxford
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-06-11T14:12:21Z
ethz.source
ECIT
ethz.identifier.importid
imp59365298d8b1123950
ethz.ecitpid
pub:146789
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-12T17:46:26Z
ethz.rosetta.lastUpdated
2019-04-04T11:38:51Z
ethz.rosetta.versionExported
true
ethz.COinS
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