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  4. A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA
 
research article

A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA

Lavery, Richard
•
Zakrzewska, Krystyna
•
Beveridge, David
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2010
Nucleic Acids Research

It is well recognized that base sequence exerts a significant influence on the properties of DNA and plays a significant role in protein-DNA interactions vital for cellular processes. Understanding and predicting base sequence effects requires an extensive structural and dynamic dataset which is currently unavailable from experiment. A consortium of laboratories was consequently formed to obtain this information using molecular simulations. This article describes results providing information not only on all 10 unique base pair steps, but also on all possible nearest-neighbor effects on these steps. These results are derived from simulations of 50-100 ns on 39 different DNA oligomers in explicit solvent and using a physiological salt concentration. We demonstrate that the simulations are converged in terms of helical and backbone parameters. The results show that nearest-neighbor effects on base pair steps are very significant, implying that dinucleotide models are insufficient for predicting sequence-dependent behavior. Flanking base sequences can notably lead to base pair step parameters in dynamic equilibrium between two conformational sub-states. Although this study only provides limited data on next-nearest-neighbor effects, we suggest that such effects should be analyzed before attempting to predict the sequence-dependent behavior of DNA.

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Type
research article
DOI
10.1093/nar/gkp834
Web of Science ID

WOS:000273229100030

Author(s)
Lavery, Richard
Zakrzewska, Krystyna
Beveridge, David
Bishop, Thomas C.
Case, David A.
Cheatham, Thomas
Dixit, Surjit
Jayaram, B.
Lankas, Filip
Laughton, Charles
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Date Issued

2010

Published in
Nucleic Acids Research
Volume

38

Start page

299

End page

313

Subjects

Nucleic-Acid Structure

•

Particle Mesh Ewald

•

Unique Tetranucleotide Sequences

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Double-Helical Dna

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Free-Energy

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Dinucleotide Steps

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Dipolar Couplings

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Force-Field

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Curved Dna

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Simulations

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LCVMM  
Available on Infoscience
December 16, 2011
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/75784
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