Kinefold web server for RNA/DNA folding path and structure prediction including pseudoknots and knots

The Kinefold web server provides a web interface for stochastic folding simulations of nucleic acids on second to minute molecular time scales. Renaturation or co-transcriptional folding paths are simulated at the level of helix formation and dissociation in agreement with the seminal experimental results. Pseudoknots and topologically ‘entangled’ helices (i.e. knots) are efficiently predicted taking into account simple geometrical and topological constraints. To encourage interactivity, simulations launched as immediate jobs are automatically stopped after a few seconds and return adapted recommendations. Users can then choose to continue incomplete simulations using the batch queuing system or go back and modify suggested options in their initial query. Detailed output provide (i) a series of low free energy structures, (ii) an online animated folding path and (iii) a programmable trajectory plot focusing on a few helices of interest to each user. The service can be accessed at .

[1]  A Xayaphoummine,et al.  Prediction and statistics of pseudoknots in RNA structures using exactly clustered stochastic simulations , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A. E. Walter,et al.  Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves predictions of RNA folding. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Weixiong Zhang,et al.  ILM: a web server for predicting RNA secondary structures with pseudoknots , 2004, Nucleic Acids Res..

[4]  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.

[5]  Paul Higgs,et al.  Evidence for kinetic effects in the folding of large RNA molecules , 1996 .

[6]  C. Pleij,et al.  Metastable structures and refolding kinetics in hok mRNA of plasmid R1. , 1999, RNA.

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

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

[9]  István Miklós,et al.  Co-transcriptional folding is encoded within RNA genes , 2004, BMC Molecular Biology.

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

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

[12]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[13]  Tatsuya Akutsu,et al.  Dynamic programming algorithms for RNA secondary structure prediction with pseudoknots , 2000, Discret. Appl. Math..

[14]  Christian N. S. Pedersen,et al.  RNA Pseudoknot Prediction in Energy-Based Models , 2000, J. Comput. Biol..

[15]  Hélène Touzet,et al.  CARNAC: folding families of related RNAs , 2004, Nucleic Acids Res..

[16]  A. Gultyaev,et al.  The computer simulation of RNA folding involving pseudoknot formation. , 1991, Nucleic acids research.

[17]  Michael Zuker,et al.  Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information , 1981, Nucleic Acids Res..

[18]  Vadim V. Demidov,et al.  Nucleic Acids: Structures, Properties and Functions , 2001 .

[19]  C. Pleij,et al.  The influence of a metastable structure in plasmid primer RNA on antisense RNA binding kinetics. , 1995, Nucleic acids research.

[20]  Niles A. Pierce,et al.  A partition function algorithm for nucleic acid secondary structure including pseudoknots , 2003, J. Comput. Chem..

[21]  C. Pleij,et al.  Dynamic competition between alternative structures in viroid RNAs simulated by an RNA folding algorithm. , 1998, Journal of molecular biology.

[22]  E Rivas,et al.  A dynamic programming algorithm for RNA structure prediction including pseudoknots. , 1998, Journal of molecular biology.

[23]  Weixiong Zhang,et al.  An Iterated loop matching approach to the prediction of RNA secondary structures with pseudoknots , 2004, Bioinform..

[24]  J. SantaLucia,et al.  A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

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

[26]  D M Crothers,et al.  Relaxation kinetics of dimer formation by self complementary oligonucleotides. , 1971, Journal of molecular biology.

[27]  J. Abrahams,et al.  Prediction of RNA secondary structure, including pseudoknotting, by computer simulation. , 1990, Nucleic acids research.

[28]  Jean-François Léger,et al.  Probing complex RNA structures by mechanical force , 2003, The European physical journal. E, Soft matter.

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

[30]  M. Waterman,et al.  RNA secondary structure: a complete mathematical analysis , 1978 .

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

[32]  E. Siggia,et al.  Modeling RNA folding paths with pseudoknots: application to hepatitis delta virus ribozyme. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Robert Giegerich,et al.  RNA Movies: Visualizing RNA secondary structure spaces , 1997, German Conference on Bioinformatics.

[34]  Jerrold R. Griggs,et al.  Algorithms for Loop Matchings , 1978 .

[35]  F. Kramer,et al.  Secondary structure formation during RNA synthesis. , 1981, Nucleic acids research.

[36]  D. Turner,et al.  Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Anne Condon,et al.  RNAsoft: a suite of RNA secondary structure prediction and design software tools , 2003, Nucleic Acids Res..

[38]  J. Conway An enumeration of knots and links, and some of their algebraic properties , 1970 .