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@ARTICLE{Hanke:885966,
      author       = {Hanke, Christian A. and Gohlke, Holger},
      title        = {{F}orce field dependence of riboswitch dynamics},
      journal      = {Methods in enzymology},
      volume       = {553},
      issn         = {0076-6879},
      address      = {New York, NY [u.a.]},
      publisher    = {Elsevier},
      reportid     = {FZJ-2020-04197},
      pages        = {163‐191},
      year         = {2015},
      abstract     = {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.},
      ddc          = {570},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1016/bs.mie.2014.10.056},
      url          = {https://juser.fz-juelich.de/record/885966},
}