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| Author(s): |
Pedro Rafael Costa
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Botucatu. 2016-08-30. |
| Institution: | Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu |
| Defense date: | 2016-08-23 |
| Advisor: | Ney Lemke |
| Abstract | |
The discovery of a wide variety of RNA sequences present in transcriptomes with unknown function has stimulated the development of experimental and computational techniques to determine the function of these molecules. However, understanding the activities of a given RNA molecule involves not only finding its minimum free energy structure, but also studying its metastable structures. The methodologies available for predicting RNA structure ignore kinetic traps that can lead to formation of suboptimal structures and are based in over-simplified thermodynamic models. These methodologies usually can not predict RNA conformations with more complex topologies, such as pseudoknots. In this work we present a computational model for cotranscriptional folding that considers the influence of RNA structures during transcription elongation. After determining the allowed conformations for the sequence of interest, the algorithm established a series of allowed reactions between these structures. The reactions rates are weighted by the Boltzmann factor based on Gibbs free energy variation between the states. The free energies for secondary structures were estimated by the nearest-neighbor model, and two algorithms were implemented to calculate the free energy of pseudoknots. Finally, Monte Carlo simulations based on the Gillespie algorithm were performed to find out the RNA folding path. We show using examples the potential of the software developed. (AU) | |
| FAPESP's process: | 12/19377-4 - Influence of the transcriptional dynamics on RNA folding |
| Grantee: | Pedro Rafael Costa |
| Support type: | Scholarships in Brazil - Doctorate |