Efficient computation of RNA folding dynamics

Barrier trees consisting of local minima and their connecting saddle points imply a natural coarse-graining for the description of the energy landscape of RNA secondary structures. Here we show that, based on this approach, it is possible to predict the folding behaviour of RNA molecules by numerical integration. Comparison with stochastic folding simulations shows reasonable agreement of the resulting folding dynamics and a drastic increase in computational efficiency that makes it possible to investigate the folding dynamics of RNA of at least tRNA size. Our approach is readily applicable to bistable RNA molecules and promises to facilitate studies on the dynamic behaviour of RNA switches.

[1]  M. Eigen,et al.  Co-operative non-enzymic base recognition. 3. Kinetics of the helix-coil transition of the oligoribouridylic--oligoriboadenylic acid system and of oligoriboadenylic acid alone at acidic pH. , 1971, Journal of molecular biology.

[2]  D. Porschke,et al.  Thermodynamic and kinetic parameters of an oligonucleotide hairpin helix. , 1974, Biophysical chemistry.

[3]  D. Gillespie.  A General Method for Numerically Simulating the Stochastic Time Evolution of Coupled Chemical Reactions , 1976 .

[4]  R Nussinov,et al.  Sequential folding of a messenger RNA molecule. , 1981, Journal of molecular biology.

[5]  David Sankoff,et al.  RNA secondary structures and their prediction , 1984 .

[6]  H. M. Martinez,et al.  An RNA folding rule , 1984, Nucleic Acids Res..

[7]  A A Mironov,et al.  A kinetic approach to the prediction of RNA secondary structures. , 1985, Journal of biomolecular structure & dynamics.

[8]  G. Toulouse,et al.  Ultrametricity for physicists , 1986 .

[9]  K. Nemoto,et al.  Metastable states of the SK spin glass model , 1988 .

[10]  M. Zuker.  On finding all suboptimal foldings of an RNA molecule. , 1989, Science.

[11]  Miguel Angel Virasoro,et al.  Energy barriers in SK-spin glass model , 1989 .

[12]  J. McCaskill.  The equilibrium partition function and base pair binding probabilities for RNA secondary structure , 1990, Biopolymers.

[13]  P. Wolynes,et al.  The energy landscapes and motions of proteins. , 1991, Science.

[14]  Critical behaviour of a surface reaction model with infinitely many absorbing states , 1993, cond-mat/9312065.

[15]  Walter Fontana,et al.  Fast folding and comparison of RNA secondary structures , 1994 .

[16]  T. H. Klotz,et al.  "Valley structures" in the phase space of a finite 3d ISING spin glass with , 1994 .

[17]  C. Pleij,et al.  The computer simulation of RNA folding pathways using a genetic algorithm. , 1995, Journal of molecular biology.

[18]  C. Biebricher,et al.  Design of artificial short-chained RNA species that are replicated by Q beta replicase. , 1995, Biochemistry.

[19]  G. Steger,et al.  Description of RNA folding by "simulated annealing". , 1996, Journal of molecular biology.

[20]  Peter F. Stadler,et al.  Dynamic Programming Algorithm for the Density of States of RNA Secondary Structures , 1996, German Conference on Bioinformatics.

[21]  Barkema,et al.  Event-Based Relaxation of Continuous Disordered Systems. , 1996, Physical review letters.

[22]  R. Poot,et al.  RNA folding kinetics regulates translation of phage MS2 maturation gene. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Onuchic,et al.  Theory of protein folding: the energy landscape perspective. , 1997, Annual review of physical chemistry.

[24]  Detlev Riesner,et al.  Viroid processing: switch from cleavage to ligation is driven by a change from a tetraloop to a loop E conformation , 1997, The EMBO journal.

[25]  E. Westhof,et al.  Hierarchy and dynamics of RNA folding. , 1997, Annual review of biophysics and biomolecular structure.

[26]  M. Karplus,et al.  The topology of multidimensional potential energy surfaces: Theory and application to peptide structure and kinetics , 1997 .

[27]  Christine Jacob,et al.  Stochastic theories of the activated complex and the activated collision: The RNA example , 1997 .

[28]  A. T. Perrotta,et al.  A toggle duplex in hepatitis delta virus self-cleaving RNA that stabilizes an inactive and a salt-dependent pro-active ribozyme conformation. , 1998, Journal of molecular biology.

[29]  Peter F. Stadler,et al.  Combinatorics of RNA Secondary Structures , 1998, Discret. Appl. Math..

[30]  Mark A. Miller,et al.  Archetypal energy landscapes , 1998, Nature.

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

[32]  P. Schuster,et al.  Complete suboptimal folding of RNA and the stability of secondary structures. , 1999, Biopolymers.

[33]  D. Bartel,et al.  One sequence, two ribozymes: implications for the emergence of new ribozyme folds. , 2000, Science.

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

[35]  D. Thirumalai,et al.  Early events in RNA folding. , 2001, Annual review of physical chemistry.

[36]  A. Roitberg,et al.  All-atom structure prediction and folding simulations of a stable protein. , 2002, Journal of the American Chemical Society.

[37]  Michael T. Wolfinger,et al.  Barrier Trees of Degenerate Landscapes , 2002 .

[38]  R. Breaker.  Engineered allosteric ribozymes as biosensor components. , 2002, Current opinion in biotechnology.

[39]  C. Pleij,et al.  Self-induced structural switches in RNA. , 2002, Biochimie.

[40]  R. Friesner.  Computational Methods for Protein Folding , 2002 .

[41]  Shi-Jie Chen,et al.  RNA hairpin-folding kinetics , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[42]  P. Wolynes,et al.  The physics and bioinformatics of binding and folding—an energy landscape perspective , 2003, Biopolymers.

[43]  J. Ponder,et al.  Force fields for protein simulations. , 2003, Advances in protein chemistry.

[44]  Robert Giegerich,et al.  Prediction of conformational switching in RNA , 2003, German Conference on Bioinformatics.

[45]  S Banu Ozkan,et al.  Computing the transition state populations in simple protein models. , 2003, Biopolymers.

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

[47]  P. Schuster,et al.  Statistics of RNA melting kinetics , 2004, European Biophysics Journal.