Folding kinetics of large RNAs

JOURNAL OF MOLECULAR BIOLOGY

卷:379

Article

Geis, Michael¹  Flamm, Christoph²  Wolfinger, Michael T.²  Tanzer, Andrea^1,2,3  Hofacker, Ivo L.²  Middendorf, Martin⁴  Mandl, Christian⁵  Stadler, Peter F.^1,2,6,7,8  Thurner, Caroline^2,5 

[1] Univ Leipzig, Interdisciplinary Ctr Bioinformat, D-04107 Leipzig, Germany

[2] Univ Vienna, Inst Theoret Chem, A-1090 Vienna, Austria

[3] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA

[4] Univ Leipzig, Parallel Comp & Complex Syst, Dept Comp Sci, D-04103 Leipzig, Germany

[5] Med Univ Vienna, Clin Inst Virol, A-1095 Vienna, Austria

[6] Univ Leipzig, Bioinformat Grp, Dept Comp Sci, D-04107 Leipzig, Germany

[7] Fraunhofer Inst Zelltherapie & Immunol, D-04103 Leipzig, Germany

[8] Santa Fe Inst, Santa Fe, NM 87501 USA

关键词: RNA folding kinetics;    co-transcriptional folding;    folding pathway;    metastable structure;    folding trajectories;   

DOI  :  10.1016/j.jmb.2008.02.064

来源: Elsevier

【 摘 要 】

We introduce here a heuristic approach to kinetic RNA folding that constructs secondary structures by stepwise combination of building blocks. These blocks correspond to subsequences and their thermodynamically optimal structures. These are determined by the standard dynamic programming approach to RNA folding. Folding trajectories are modeled at base-pair resolution using the Morgan-Higgs heuristic and a barrier tree-based heuristic to connect combinations of the local building blocks. Implemented in the program Kinwalker, the algorithm allows co-transcriptional folding and can be used to fold sequences of up to about 1500 nucleotides in length. A detailed comparison with several well-studied examples from the literature, including the delayed folding of bacteriophage cloverleaf structures, the adenine sensing riboswitch, and the hok RNA, shows an excellent agreement of predicted trajectories and experimental evidence. The software is available as part of the ViennaRNA Package. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

Free