Authors: Xinyu Tang, Shawna Thomas, Lydia Tapia, Nancy M. Amato

Venue: In. Proc. International Conference on Research in Computational Molecular Biology
DOI: 10.1007/978-3-540-71681-5_19
Link to Publication

Abstract:
It has recently been found that some RNA functions are determined by the actual folding kinetics and not just the RNA’s nucleotide sequence or its native structure. We present new computational tools for simulating and analyzing RNA folding kinetic metrics such as population kinetics, folding rates, and the folding of particular subsequences. Our method first builds an approximate representation (called a map) of the RNA’s folding energy landscape, and then uses specialized analysis techniques to extract folding kinetics from the map. We provide a new sampling strategy called Probabilistic Boltzmann Sampling (PBS) that enables us to approximate the folding landscape with much smaller maps, typically by several orders of magnitude. We also describe a new analysis technique, Map-based Monte Carlo (MMC) simulation, to stochastically extract folding pathways from the map. We demonstrate that our technique can be applied to large RNA (e.g., 200+ nucleotides), where representing the full landscape is infeasible, and that our tools provide results comparable to other simulation methods that work on complete energy landscapes. We present results showing that our approach computes the same relative functional rates as seen in experiments for the relative plasmid replication rates of ColE1 RNAII and its mutants, and for the relative gene expression rates of MS2 phage RNA and its mutants. 

@inproceedings{Tang-tfsaar-2007, 
 address = {Berlin, Heidelberg}, 
 author = {Tang, Xinyu 
and Thomas, Shawna 
and Tapia, Lydia 
and Amato, Nancy M.}, 
 booktitle = {Research in Computational Molecular Biology}, 
 editor = {Speed, Terry 
and Huang, Haiyan}, 
 isbn = {978-3-540-71681-5}, 
 pages = {268--282}, 
 publisher = {Springer Berlin Heidelberg}, 
 title = {Tools for Simulating and Analyzing RNA Folding Kinetics}, 
 year = {2007} 
}