Integrating molecular dynamics simulations with chemical probing experiments using SHAPE-FIT.
Integration and calibration of molecular dynamics simulations with experimental data remain a challenging endeavor. We have developed a novel method to integrate chemical probing experiments with molecular simulations of RNA molecules by using a native structure-based model. Selective 2'-hydroxyl acylation by primer extension (SHAPE) characterizes the mobility of each residue in the RNA. Our method, SHAPE-FIT, automatically optimizes the potential parameters of the force field according to measured reactivities from SHAPE. The optimized parameter set allows simulations of dynamics highly consistent with SHAPE probing experiments. Such atomistic simulations, thoroughly grounded in experiment, can open a new window on RNA structure-function relations.
New Mexico Consortium, Los Alamos, New Mexico, USA; Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA. Electronic address: serdal@lanl.gov.
Serdal
S
Kirmizialtin
New Mexico Consortium, Los Alamos, New Mexico, USA; Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Scott P
SP
Hennelly
Steinbuch Centre for Computing, Karlsruhe Institute of Technology, Karlsruhe, Germany.
Alexander
A
Schug
Center for Theoretical Biological Physics, Rice University, Houston, Texas, USA; Department of Physics and Astronomy, Rice University, Houston, Texas, USA; Department of Chemistry, Rice University, Houston, Texas, USA; Department of Biosciences, Rice University, Houston, Texas, USA; Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, USA.
Jose N
JN
Onuchic
New Mexico Consortium, Los Alamos, New Mexico, USA; Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA. Electronic address: kys@lanl.gov.
Karissa Y
KY
Sanbonmatsu
D000215:Acylation; D019295:Computational Biology / Q000379:methods*; D017665:Hydroxyl Radical / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*
D008024:Ligands; D017665:Hydroxyl Radical; D012313:RNA
Modeling; Molecular dynamics simulation; RNA; Riboswitch; SHAPE