TY - GEN
T1 - Tools for simulating and analyzing RNA folding kinetics
AU - Tang, Xinyu
AU - Thomas, Shawna
AU - Tapia, Lydia
AU - Amato, Nancy M.
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
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U2 - 10.1007/978-3-540-71681-5_19
DO - 10.1007/978-3-540-71681-5_19
M3 - Conference contribution
AN - SCOPUS:34547442884
SN - 3540716807
SN - 9783540716808
T3 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
SP - 268
EP - 282
BT - Research in Computational Molecular Biology - 11th Annual International Conference, RECOMB 2007, Proceedings
PB - Springer
T2 - 11th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2007
Y2 - 21 April 2007 through 25 April 2007
ER -