Decoding Single Molecule Time Traces with Dynamic Disorder

Single molecule time trajectories of biomolecules provide glimpses into complex folding landscapes that are difficult to visualize using conventional ensemble measurements. Recent experiments and theoretical analyses have highlighted dynamic disorder in certain classes of biomolecules, whose dynamic...

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Bibliographic Details
Published in:PLoS computational biology 2016-12, Vol.12 (12), p.e1005286-e1005286
Main Authors: Hwang, Wonseok, Lee, Il-Buem, Hong, Seok-Cheol, Hyeon, Changbong
Format: Article
Language:English
Subjects:
Accuracy
Algorithms
Analysis
Clustering
Computer and Information Sciences
Computer Simulation
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - ultrastructure
Experiments
Fluorescence Resonance Energy Transfer - methods
Funding
Hydraulics
Kinetics
Markov processes
Mathematical models
Models, Chemical
Models, Molecular
Physical Sciences
Protein folding
Research and Analysis Methods
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Summary:Single molecule time trajectories of biomolecules provide glimpses into complex folding landscapes that are difficult to visualize using conventional ensemble measurements. Recent experiments and theoretical analyses have highlighted dynamic disorder in certain classes of biomolecules, whose dynamic pattern of conformational transitions is affected by slower transition dynamics of internal state hidden in a low dimensional projection. A systematic means to analyze such data is, however, currently not well developed. Here we report a new algorithm-Variational Bayes-double chain Markov model (VB-DCMM)-to analyze single molecule time trajectories that display dynamic disorder. The proposed analysis employing VB-DCMM allows us to detect the presence of dynamic disorder, if any, in each trajectory, identify the number of internal states, and estimate transition rates between the internal states as well as the rates of conformational transition within each internal state. Applying VB-DCMM algorithm to single molecule FRET data of H-DNA in 100 mM-Na+ solution, followed by data clustering, we show that at least 6 kinetic paths linking 4 distinct internal states are required to correctly interpret the duplex-triplex transitions of H-DNA.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1005286