title: Probing RNA Native Conformational Ensembles with Structural Constraints.
abstract: Noncoding ribonucleic acids (RNA) play a critical role in a wide variety of cellular processes, ranging from regulating gene expression to post-translational modification and protein synthesis. Their activity is modulated by highly dynamic exchanges between three-dimensional conformational substates, which are difficult to characterize experimentally and computationally. Here, we present an innovative, entirely kinematic computational procedure to efficiently explore the native ensemble of RNA molecules. Our procedure projects degrees of freedom onto a subspace of conformation space defined by distance constraints in the tertiary structure. The dimensionality reduction enables efficient exploration of conformational space. We show that the conformational distributions obtained with our method broadly sample the conformational landscape observed in NMR experiments. Compared to normal mode analysis-based exploration, our procedure diffuses faster through the experimental ensemble while also accessing conformational substates to greater precision. Our results suggest that conformational sampling with a highly reduced but fully atomistic representation of noncoding RNA expresses key features of their dynamic nature.
authors.affiliation: 1 INRIA Saclay-Île de France, Bâtiment Alan Turing, Campus de l'École Polytechnique , Palaiseau, France .|2 Laboratoire d'Informatique de l'École Polytechnique (LIX), CNRS UMR 7161, École Polytechnique , Palaiseau, France .|3 Department of Computer Science, University of Copenhagen , Nørre Campus, Copenhagen, Denmark .
authors.forename: Rasmus
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: 4 Biosciences Division, SLAC National Accelerator Laboratory, Stanford University , Menlo Park, California.
authors.forename: Henry
authors.initials: H
authors.lastname: van den Bedem
authors.affiliation: 1 INRIA Saclay-Île de France, Bâtiment Alan Turing, Campus de l'École Polytechnique , Palaiseau, France .|2 Laboratoire d'Informatique de l'École Polytechnique (LIX), CNRS UMR 7161, École Polytechnique , Palaiseau, France .
authors.forename: Julie
authors.initials: J
authors.lastname: Bernauer
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*
chemical_list: D012313:RNA
keywords: combinatorial optimization; computational molecular biology; protein folding