Abstract: Using the Fast Fourier Transform to Accelerate the Computational Search for RNA Conformational Switches

We describe the broad outline of a new thermodynamics-based algorithm, FFTbor, that uses the fast Fourier transform to perform polynomial interpolation to compute the Boltzmann probability that secondary structures differ by k base pairs from an arbitrary reference structure of a given RNA sequence. The algorithm, which runs in quartic time O(n4) and quadratic space O(n2), is used to determine the correlation between kinetic folding speed and the ruggedness of the energy landscape, and to predict the location of riboswitch expression platform candidates. The full paper appears in PLoS ONE (2012) 19 Dec 2012. A web server is available at http://bioinformatics.bc.edu/clotelab/FFTbor/.

[1]  Peter Clote,et al.  Maximum expected accuracy structural neighbors of an RNA secondary structure , 2012, BMC Bioinformatics.

[2]  Peter Clote,et al.  Boltzmann probability of RNA structural neighbors and riboswitch detection , 2007, Bioinform..

[3]  P. Schuster,et al.  RNA folding at elementary step resolution. , 1999, RNA.

[4]  P. Stadler,et al.  Design of multistable RNA molecules. , 2001, RNA.

[5]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[6]  R. Breaker,et al.  Adenine riboswitches and gene activation by disruption of a transcription terminator , 2004, Nature Structural &Molecular Biology.

[7]  P. Clote,et al.  Computing folding pathways between RNA secondary structures , 2009, Nucleic acids research.

[8]  Hsien-Da Huang,et al.  Computational identification of riboswitches based on RNA conserved functional sequences and conformations. , 2009, RNA.

[9]  Klara Kedem,et al.  STR2: A structure to string approach for locating G-box riboswitch shapes in pre-selected genes , 2004, Silico Biol..

[10]  Sean R. Eddy,et al.  Infernal 1.0: inference of RNA alignments , 2009, Bioinform..

[11]  Sean R. Eddy,et al.  Infernal 1.0: inference of RNA alignments , 2009, Bioinform..

[12]  Yann Ponty,et al.  An Unbiased Adaptive Sampling Algorithm for the Exploration of RNA Mutational Landscapes Under Evolutionary Pressure , 2011, J. Comput. Biol..

[13]  Robert D. Finn,et al.  Rfam: Wikipedia, clans and the “decimal” release , 2010, Nucleic Acids Res..

[14]  Srinivas Devadas,et al.  Efficient Algorithms for Probing the RNA Mutation Landscape , 2008, PLoS Comput. Biol..

[15]  Peter Clote,et al.  Energy landscape of k-point mutants of an RNA molecule , 2005, Bioinform..

[16]  Steven G. Johnson,et al.  The Design and Implementation of FFTW3 , 2005, Proceedings of the IEEE.

[17]  V. Moulton,et al.  Predicting RNA Structure Using Mutual Information , 2005, Applied bioinformatics.

[18]  C. Lawrence,et al.  A statistical sampling algorithm for RNA secondary structure prediction. , 2003, Nucleic acids research.

[19]  D. Turner,et al.  Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson-Crick base pairs. , 1998, Biochemistry.

[20]  Anne Condon,et al.  A new algorithm for RNA secondary structure design. , 2004, Journal of molecular biology.

[21]  Niles A. Pierce,et al.  Nucleic acid sequence design via efficient ensemble defect optimization , 2011, J. Comput. Chem..

[22]  J. Sabina,et al.  Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. , 1999, Journal of molecular biology.

[23]  R. Breaker,et al.  Riboswitches as versatile gene control elements. , 2005, Current opinion in structural biology.

[24]  J. Hartigan,et al.  The Dip Test of Unimodality , 1985 .

[25]  R. Nussinov,et al.  Fast algorithm for predicting the secondary structure of single-stranded RNA. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. Mann,et al.  Phosphotyrosine interactome of the ErbB-receptor kinase family , 2005, Molecular systems biology.

[27]  A. Serganov,et al.  Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs. , 2004, Chemistry & biology.

[28]  Rolf Backofen,et al.  INFO-RNA - a fast approach to inverse RNA folding , 2006, Bioinform..

[29]  P. Wolynes.  Energy landscapes and solved protein–folding problems , 2004, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[30]  Thomas F Knight.  Engineering novel life , 2005, Molecular systems biology.

[31]  S. Altschul,et al.  Significance of nucleotide sequence alignments: a method for random sequence permutation that preserves dinucleotide and codon usage. , 1985, Molecular biology and evolution.

[32]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

[33]  J. Onuchic,et al.  Funnels, pathways, and the energy landscape of protein folding: A synthesis , 1994, Proteins.

[34]  Thomas Dandekar,et al.  Riboswitch finder tool for identification of riboswitch RNAs , 2004, Nucleic Acids Res..

[35]  Drew Endy,et al.  Engineering BioBrick vectors from BioBrick parts , 2008, Journal of Biological Engineering.

[36]  Jeffrey E. Barrick,et al.  Riboswitches Control Fundamental Biochemical Pathways in Bacillus subtilis and Other Bacteria , 2003, Cell.

[37]  N. Higham.  The numerical stability of barycentric Lagrange interpolation , 2004 .

[38]  Torsten Waldminghaus,et al.  Generation of synthetic RNA-based thermosensors , 2008, Biological chemistry.

[39]  Pradipta Bandyopadhyay,et al.  Riboswitch Detection Using Profile Hidden Markov Models , 2009, BMC Bioinformatics.

[40]  Enrique Merino,et al.  RibEx: a web server for locating riboswitches and other conserved bacterial regulatory elements , 2005, Nucleic Acids Res..