Home > External Publications > Vita Publications > Force field dependence of riboswitch dynamics > print

001     885966
005     20201102075617.0
024 7 _ |2 doi
|a 10.1016/bs.mie.2014.10.056
037 _ _ |a FZJ-2020-04197
082 _ _ |a 570
100 1 _ |0 P:(DE-HGF)0
|a Hanke, Christian A.
|b 0
245 _ _ |a Force field dependence of riboswitch dynamics
260 _ _ |a New York, NY [u.a.]
|b Elsevier
|c 2015
336 7 _ |2 DRIVER
|a article
336 7 _ |2 DataCite
|a Output Types/Journal article
336 7 _ |0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
|a Journal Article
|b journal
|m journal
|s 1603963311_13182
336 7 _ |2 BibTeX
|a ARTICLE
336 7 _ |2 ORCID
|a JOURNAL_ARTICLE
336 7 _ |0 0
|2 EndNote
|a Journal Article
520 _ _ |a Riboswitches are noncoding regulatory elements that control gene expression in response to the presence of metabolites, which bind to the aptamer domain. Metabolite binding appears to occur through a combination of conformational selection and induced fit mechanism. This demands to characterize the structural dynamics of the apo state of aptamer domains. In principle, molecular dynamics (MD) simulations can give insights at the atomistic level into the dynamics of the aptamer domain. However, it is unclear to what extent contemporary force fields can bias such insights. Here, we show that the Amber force field ff99 yields the best agreement with detailed experimental observations on differences in the structural dynamics of wild type and mutant aptamer domains of the guanine-sensing riboswitch (Gsw), including a pronounced influence of $Mg^{2+}$. In contrast, applying ff99 with parmbsc0 and parm$χ_{OL}$ modifications (denoted ff10) results in strongly damped motions and overly stable tertiary loop–loop interactions. These results are based on 58 MD simulations with an aggregate simulation time > 11 $μs$, careful modeling of $Mg^{2+}$ ions, and thorough statistical testing. Our results suggest that the moderate stabilization of the $χ$-anti region in ff10 can have an unwanted damping effect on functionally relevant structural dynamics of marginally stable RNA systems. This suggestion is supported by crystal structure analyses of Gsw aptamer domains that reveal $χ$ torsions with high-anti values in the most mobile regions. We expect that future RNA force field development will benefit from considering marginally stable RNA systems and optimization toward good representations of dynamics in addition to structural characteristics.
700 1 _ |0 P:(DE-Juel1)172663
|a Gohlke, Holger
|b 1
|u fzj
773 _ _ |0 PERI:(DE-600)2221516-5
|a 10.1016/bs.mie.2014.10.056
|p 163‐191
|t Methods in enzymology
|v 553
|x 0076-6879
|y 2015
909 C O |o oai:juser.fz-juelich.de:885966
|p extern4vita
910 1 _ |0 I:(DE-588b)5008462-8
|6 P:(DE-Juel1)172663
|a Forschungszentrum Jülich
|b 1
|k FZJ
915 _ _ |0 StatID:(DE-HGF)0300
|2 StatID
|a DBCoverage
|b Medline
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)0310
|2 StatID
|a DBCoverage
|b NCBI Molecular Biology Database
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)0199
|2 StatID
|a DBCoverage
|b Clarivate Analytics Master Journal List
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)1120
|2 StatID
|a DBCoverage
|b BIOSIS Reviews Reports And Meetings
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)0110
|2 StatID
|a WoS
|b Science Citation Index
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)0150
|2 StatID
|a DBCoverage
|b Web of Science Core Collection
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)0111
|2 StatID
|a WoS
|b Science Citation Index Expanded
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)0160
|2 StatID
|a DBCoverage
|b Essential Science Indicators
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)1050
|2 StatID
|a DBCoverage
|b BIOSIS Previews
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)0100
|2 StatID
|a JCR
|b METHOD ENZYMOL : 2018
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)0200
|2 StatID
|a DBCoverage
|b SCOPUS
|d 2019-12-21
915 _ _ |0 StatID:(DE-HGF)9900
|2 StatID
|a IF < 5
|d 2019-12-21
980 1 _ |a EXTERN4VITA
980 _ _ |a journal
980 _ _ |a USER
980 _ _ |a I:(DE-Juel1)JSC-20090406

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21