H. Isambert et Ed. Siggia, Modeling RNA folding paths with pseudoknots: Application to hepatitis delta virus ribozyme, P NAS US, 97(12), 2000, pp. 6515-6520
Citations number
31
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
A quantitative understanding of nucleic: acid hybridization is essential to
many aspects of biotechnology, such as DNA microarrays, as well as to the
structure and folding kinetics of RNA. However, predictions of nucleic acid
secondary structures have long been impeded by the presence of helices int
erior to loops, so-called pseudoknots, which impose complex three-dimension
al conformational constraints. In this paper we compute the pseudoknot free
energies analytically in terms of known standard parameters, and we show h
ow the results can be included in a kinetic Monte Carlo code to follow the
succession of secondary structures during quenched or sequential folding. F
or the hepatitis delta virus ribozyme, we predict several nonnative stems o
n the folding path, characterize a kinetically trapped state, interpret sev
eral experimentally characterized mutations in terms of the folding path, a
nd suggest how hybridization with other parts of the genome inactivates the
newly formed ribozyme.