Reduced model captures Mg(2+)-RNA interaction free energy of riboswitches.
The stability of RNA tertiary structures depends heavily on Mg(2+). The Mg(2+)-RNA interaction free energy that stabilizes an RNA structure can be computed experimentally through fluorescence-based assays that measure Γ2+, the number of excess Mg(2+) associated with an RNA molecule. Previous explicit-solvent simulations predict that the majority of excess Mg(2+) ions interact closely and strongly with the RNA, unlike monovalent ions such as K(+), suggesting that an explicit treatment of Mg(2+) is important for capturing RNA dynamics. Here we present a reduced model that accurately reproduces the thermodynamics of Mg(2+)-RNA interactions. This model is able to characterize long-timescale RNA dynamics coupled to Mg(2+) through the explicit representation of Mg(2+) ions. KCl is described by Debye-Hückel screening and a Manning condensation parameter, which represents condensed K(+) and models its competition with condensed Mg(2+). The model contains one fitted parameter, the number of condensed K(+) ions in the absence of Mg(2+). Values of Γ2+ computed from molecular dynamics simulations using the model show excellent agreement with both experimental data on the adenine riboswitch and previous explicit-solvent simulations of the SAM-I riboswitch. This agreement confirms the thermodynamic accuracy of the model via the direct relation of Γ2+ to the Mg(2+)-RNA interaction free energy, and provides further support for the predictions from explicit-solvent calculations. This reduced model will be useful for future studies of the interplay between Mg(2+) and RNA dynamics.
Center for Theoretical Biological Physics and Department of Physics and Astronomy, Rice University, Houston, Texas.
Ryan L
RL
Hayes
Center for Theoretical Biological Physics and Department of Physics and Astronomy, Rice University, Houston, Texas.
Jeffrey K
JK
Noel
Department of Physics, Northeastern University, Boston, Massachusetts.
Paul C
PC
Whitford
Department of Chemistry, Boston College, Chestnut Hill, Massachusetts.
Udayan
U
Mohanty
Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Labs, Los Alamos, New Mexico. Electronic address: kys@lanl.gov.
Karissa Y
KY
Sanbonmatsu
Center for Theoretical Biological Physics and Department of Physics and Astronomy, Rice University, Houston, Texas; Department of Chemistry and Department of Biochemistry and Cell Biology, Rice University, Houston, Texas. Electronic address: jonuchic@rice.edu.
José N
JN
Onuchic
D001483:Base Sequence; D002138:Calibration; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017711:Nonlinear Dynamics; D009690:Nucleic Acid Conformation; D011188:Potassium / Q000737:chemistry; D058928:Riboswitch; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
D058928:Riboswitch; D012997:Solvents; D008274:Magnesium; D011188:Potassium