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. 2008 Sep;89(9):722-31.
doi: 10.1002/bip.21000.

Multiscale modeling of nucleic acids: insights into DNA flexibility

Yannick J Bomble  1 , David A Case
Affiliations

Multiscale modeling of nucleic acids: insights into DNA flexibility

Yannick J Bomble et al. Biopolymers. 2008 Sep.

Abstract

The elastic rod theory is used together with all-atom normal mode analysis in implicit solvent to characterize the mechanical flexibility of duplex DNA. The bending, twisting, stretching rigidities extracted from all-atom simulations (on linear duplexes from 60 to 150 base pairs in length and from 94-bp minicircles) are in reasonable agreement with experimental results. We focus on salt concentration and sequence effects on the overall flexibility. Bending persistence lengths are about 20% higher than most experimental estimates, but the transition from low-salt to high-salt behavior is reproduced well, as is the dependence of the stretching modulus on salt (which is opposite to that of bending). CTG and CGG trinucleotide repeats, responsible for several degenerative disorders, are found to be more flexible than random DNA, in agreement with several recent studies, whereas poly(dA).poly(dT) is the stiffest sequence we have encountered. The results suggest that current all-atom potentials, which were parameterized on small molecules and short oligonucleotides, also provide a useful description of duplex DNA at much longer length scales.

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Figures

Figure 1
Figure 1
Low-frequency bending modes of a 150-bp linear segment of DNA. The arrows define the main motions associated with the corresponding vibration. There are nearly degenerate modes corresponding to each of these, but with displacements perpendicular to the plane of figure.
Figure 2
Figure 2
Low-frequency stretching modes of a 150-bp linear segment of DNA. The arrows define the main motions associated with the corresponding vibration.
Figure 3
Figure 3
Low-frequency twisting modes of a 150-bp linear segment of DNA. The arrows define the main motions associated with the corresponding vibration.
Figure 4
Figure 4
Low-frequency - in and out of plane bending - modes of circular DNA. The arrows define the main motions associated with the corresponding vibration. Bending motions corresponding to n=0 and n=1 do not exist in the analytical model,, so the first allowed bending comes for n=2.
Figure 5
Figure 5
Low-frequency - torsional - modes of circular DNA. The arrows define the main motions associated with the corresponding vibration.
Figure 6
Figure 6
Comparison of the persistence lengths from experiment and extracted from the elastic rod model for the d(GACT)4 sequence as a function of salt concentration at 300K.
Figure 7
Figure 7
Comparison of the stretching moduli from experiment and extracted from the elastic rod model for the d(GACT)4 sequence as a function of salt concentration at 300K.
Figure 8
Figure 8
Comparison of the persistence lengths for various GACT repeat sequences as a function of salt concentration at 300K..
Figure 9
Figure 9
Comparison of the stretching moduli for various GACT repeat sequences as a function of salt concentration at 300K.
Figure 10
Figure 10
Comparison of the twisting moduli for various GACT repeat sequences as a function of salt concentration at 300K.
Figure 11
Figure 11
Comparison of the persistence lengths for various DNA sequences with a salt concentration of 0.05M and T=300K.
Figure 12
Figure 12
Comparison of stretching moduli for various DNA sequences with a salt concentration of 0.05M and T=300K.
Figure 13
Figure 13
Comparison of twisting moduli for various DNA sequences with a salt concentration of 0.05M and T=300K.
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References

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