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Biophys. J. BioFAST: First Published November 4, 2005. doi:10.1529/biophysj.105.062935
© 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. 1. General Folding Kinetics Analysis

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 27 September 2005


  Abstract
Depending on the nucleotide sequence and the temperature and other conditions, RNA hairpin folding kinetics can be very complex. The complexity with a wide range of cooperative and noncooperative kinetic behaviors arises from the interplay between the formation of the loops, the disruption of the misfolded states, and the formation of the rate-limiting base stacks. With a rate constant model and a kinetic cluster theory, we explore the broad landscape for RNA hairpin folding kinetics. The model is validated through direct tests against several experimental measurements. The general folding kinetic mechanisms and the predicted great variety of folding kinetics are directly applicable and quantitatively testable in experiments. The results from the present study suggest that (1) previous experimental findings based on the individual hairpins revealed only a small fraction of much broader and more complex RNA hairpin folding landscapes, (2) even for structures as simple as hairpins, universal folding time scale and pathways do not exist, and (3) to treat the loop size as the sole factor to determine the hairpin folding rate is an oversimplification.

Key Words: biopolymer theory, energy landscape, folding kinetics




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Copyright © 2005 by the Biophysical Society.