A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA.
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.
Institut de Biologie et Chimie des Protéines, CNRS UMR 5086/Université de Lyon, Lyon, France. richard.lavery@ibcp.fr
Richard
R
Lavery
Krystyna
K
Zakrzewska
David
D
Beveridge
Thomas C
TC
Bishop
David A
DA
Case
Thomas
T
Cheatham
Surjit
S
Dixit
B
B
Jayaram
Filip
F
Lankas
Charles
C
Laughton
John H
JH
Maddocks
Alexis
A
Michon
Roman
R
Osman
Modesto
M
Orozco
Alberto
A
Perez
Tanya
T
Singh
Nada
N
Spackova
Jiri
J
Sponer
D020029:Base Pairing; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009711:Nucleotides / Q000737:chemistry
D009711:Nucleotides; D004247:DNA