Identifying physical causes of apparent enhanced cyclization of short DNA molecules with a coarse-grained model
File(s)
Accepted version
Author(s)
Harrison, Ryan M
Romano, Flavio
Ouldridge, Thomas E
Louis, Ard A
Doye, Jonathan PK
Type
Journal Article
Abstract
DNA cyclization is a powerful technique to gain insight into the nature of DNA bending. While the worm-like chain model provides a good description of small to moderate bending fluctuations, it is expected to break down for large bending. Recent cyclization experiments on strongly-bent shorter molecules indeed suggest enhanced flexibility over and above that expected from the worm-like chain. Here, we use a coarse-grained model of DNA to investigate the subtle thermodynamics of DNA cyclization for molecules ranging from 30 to 210 base pairs. As the molecules get shorter we find increasing deviations between our computed equilibrium j-factor and the classic worm-like chain predictions of Shimada and Yamakawa for a torsionally aligned looped molecule. These deviations are due to sharp kinking, first at nicks, and only subsequently in the body of the duplex. At the shortest lengths, substantial fraying at the ends of duplex domains is the dominant method of relaxation. We also estimate the dynamic j-factor measured in recent FRET experiments. We find that the dynamic j-factor is systematically larger than its equilibrium counterpart - with the deviation larger for shorter molecules - because not all the stress present in the fully cyclized state is present in the transition state. These observations are important for the interpretation of recent cyclization experiments, suggesting that measured anomalously high j-factors may not necessarily indicate non-WLC behavior in the body of duplexes.
Date Issued
2019-08-13
Date Acceptance
2019-07-01
Citation
Journal of Chemical Theory and Computation, 2019, 15 (8), pp.4660-4672
ISSN
1549-9618
Publisher
American Chemical Society
Start Page
4660
End Page
4672
Journal / Book Title
Journal of Chemical Theory and Computation
Volume
15
Issue
8
Copyright Statement
© 2019 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jctc.9b00112.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31282669
Subjects
Science & Technology
Physical Sciences
Chemistry, Physical
Physics, Atomic, Molecular & Chemical
Chemistry
Physics
RING-CLOSURE
CIRCULAR DNA
DOUBLE HELIX
FREE-ENERGY
IN-VITRO
FLEXIBILITY
SEQUENCE
SIMULATIONS
ELASTICITY
FRAGMENTS
Base Pairing
Cyclization
DNA, Circular
Elasticity
Models, Molecular
Monte Carlo Method
Nucleic Acid Conformation
Thermodynamics
DNA, Circular
Monte Carlo Method
Nucleic Acid Conformation
Base Pairing
Cyclization
Elasticity
Thermodynamics
Models, Molecular
q-bio.BM
q-bio.BM
Chemical Physics
0307 Theoretical and Computational Chemistry
0803 Computer Software
0601 Biochemistry and Cell Biology
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-07-08