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Title: An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization

Abstract

A new 3-Site-Per-Nucleotide coarse-grained model for DNA is presented. The model includes anisotropic potentials between bases involved in base stacking and base pair interactions that enable the description of relevant structural properties, including the major and minor grooves. In an improvement over available coarse-grained models, the correct persistence length is recovered for both ssDNA and dsDNA, allowing for simulation of non-canonical structures such as hairpins. DNA melting temperatures, measured for duplexes and hairpins by integrating over free energy surfaces generated using metadynamics simulations, are shown to be in quantitative agreement with experiment for a variety of sequences and conditions. Hybridization rate constants, calculated using forward-flux sampling, are also shown to be in good agreement with experiment. The coarse-grained model presented here is suitable for use in biological and engineering applications, including nucleosome positioning and DNA-templated engineering.

Authors:
; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science - Office of Basic Energy Sciences - Materials Sciences and Engineering Division
OSTI Identifier:
1395033
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
Journal of Chemical Physics
Additional Journal Information:
Journal Volume: 139; Journal Issue: 14; Journal ID: ISSN 0021-9606
Publisher:
American Institute of Physics (AIP)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Hinckley, Daniel M., Freeman, Gordon S., Whitmer, Jonathan K., and de Pablo, Juan J. An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization. United States: N. p., 2013. Web. doi:10.1063/1.4822042.
Hinckley, Daniel M., Freeman, Gordon S., Whitmer, Jonathan K., & de Pablo, Juan J. An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization. United States. doi:10.1063/1.4822042.
Hinckley, Daniel M., Freeman, Gordon S., Whitmer, Jonathan K., and de Pablo, Juan J. Mon . "An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization". United States. doi:10.1063/1.4822042.
@article{osti_1395033,
title = {An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization},
author = {Hinckley, Daniel M. and Freeman, Gordon S. and Whitmer, Jonathan K. and de Pablo, Juan J.},
abstractNote = {A new 3-Site-Per-Nucleotide coarse-grained model for DNA is presented. The model includes anisotropic potentials between bases involved in base stacking and base pair interactions that enable the description of relevant structural properties, including the major and minor grooves. In an improvement over available coarse-grained models, the correct persistence length is recovered for both ssDNA and dsDNA, allowing for simulation of non-canonical structures such as hairpins. DNA melting temperatures, measured for duplexes and hairpins by integrating over free energy surfaces generated using metadynamics simulations, are shown to be in quantitative agreement with experiment for a variety of sequences and conditions. Hybridization rate constants, calculated using forward-flux sampling, are also shown to be in good agreement with experiment. The coarse-grained model presented here is suitable for use in biological and engineering applications, including nucleosome positioning and DNA-templated engineering.},
doi = {10.1063/1.4822042},
journal = {Journal of Chemical Physics},
issn = {0021-9606},
number = 14,
volume = 139,
place = {United States},
year = {2013},
month = {10}
}

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