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Kinetic partitioning mechanism of HDV ribozyme folding

Journal Article · · Journal of Chemical Physics
DOI:https://doi.org/10.1063/1.4861037· OSTI ID:22255284
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  1. Department of Physics, Wuhan University, Wuhan, Hubei 430072 (China)
RNA folding kinetics is directly tied to RNA biological functions. We introduce here a new approach for predicting the folding kinetics of RNA secondary structure with pseudoknots. This approach is based on our previous established helix-based method for predicting the folding kinetics of RNA secondary structure. In this approach, the transition rates for an elementary step: (1) formation, (2) disruption of a helix stem, and (3) helix formation with concomitant partial melting of an incompatible helix, are calculated with the free energy landscape. The folding kinetics of the Hepatitis delta virus (HDV) ribozyme and the mutated sequences are studied with this method. The folding pathways are identified by recursive searching the states with high net flux-in(out) population starting from the native state. The theory results are in good agreement with that of the experiments. The results indicate that the bi-phasic folding kinetics for the wt HDV sequence is ascribed to the kinetic partitioning mechanism: Part of the population will quickly fold to the native state along the fast pathway, while another part of the population will fold along the slow pathway, in which the population is trapped in a non-native state. Single mutation not only changes the folding rate but also the folding pathway.
OSTI ID:
22255284
Journal Information:
Journal of Chemical Physics, Journal Name: Journal of Chemical Physics Journal Issue: 2 Vol. 140; ISSN JCPSA6; ISSN 0021-9606
Country of Publication:
United States
Language:
English