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Biophys. J. BioFAST: First Published November 4, 2005. doi:10.1529/biophysj.105.062950
© 2005 by the Biophysical Society.

A more recent version of this article appeared on February 1, 2006.
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BIOPHYSICAL THEORY AND MODELING

Exploring the Complex Folding Kinetics of RNA Hairpins. 2. Effect of Sequence, Length, and Misfolded States

Wenbing Zhang 1 and Shi-Jie Chen 2*

1 University of Missouri-Columbia
2 University Of Missouri-Columbia

* To whom correspondence should be addressed. E-mail: chenshi{at}missouri.edu.

Submitted on March 14, 2005
Revised on April 24, 2005
Accepted on 30 September 2005


  Abstract
The complexity of RNA hairpin folding arises from the interplay between the loop formation, the disruption of the slow-breaking misfolded states, and the formation of the slow-forming native base stacks. We investigate the general physical mechanism for the dependence of the RNA hairpin folding kinetics on the sequence and the length of the hairpin loop and the helix stem. For example, (1) the folding would slow down when a stable GC base pair moves to the middle of the stem, (2) hairpin with GC base pair near the loop would fold/unfold faster than the one with GC near the tail of the stem, (3) within certain range of the stem length, longer stem can cause faster folding, and (4) certain misfolded states can assist folding through the formation of scaffold structures to lower the entropic barrier for the folding. All our findings are directly applicable and quantitatively testable in experiments. In addition, our results can be useful for molecular design to achieve desirable fast/slow-folding hairpins, hairpins with/without specific misfolded intermediates, and hairpins that fold along designed pathways.

Key Words: biopolymer theory, energy landscape, folding kinetics




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Copyright © 2005 by the Biophysical Society.