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Comparative Study
. 2003 Nov;85(5):2872-83.
doi: 10.1016/S0006-3495(03)74710-9.

DNA basepair step deformability inferred from molecular dynamics simulations

Filip Lankas  1 , Jirí Sponer, Jörg Langowski, Thomas E Cheatham 3rd
Affiliations
Comparative Study

DNA basepair step deformability inferred from molecular dynamics simulations

Filip Lankas et al. Biophys J. 2003 Nov.

Abstract

The sequence-dependent DNA deformability at the basepair step level was investigated using large-scale atomic resolution molecular dynamics simulation of two 18-bp DNA oligomers: d(GCCTATAAACGCCTATAA) and d(CTAGGTGGATGACTCATT). From an analysis of the structural fluctuations, the harmonic potential energy functions for all 10 unique steps with respect to the six step parameters have been evaluated. In the case of roll, three distinct groups of steps have been identified: the flexible pyrimidine-purine (YR) steps, intermediate purine-purine (RR), and stiff purine-pyrimidine (RY). The YR steps appear to be the most flexible in tilt and partially in twist. Increasing stiffness from YR through RR to RY was observed for rise, whereas shift and slide lack simple trends. A proposed measure of the relative importance of couplings identifies the slide-rise, twist-roll, and twist-slide couplings to play a major role. The force constants obtained are of similar magnitudes to those based on a crystallographic ensemble. However, the current data have a less complicated and less pronounced sequence dependence. A correlation analysis reveals concerted motions of neighboring steps and thus exposes limitations in the dinucleotide model. The comparison of DNA deformability from this and other studies with recent quantum-chemical stacking energy calculations suggests poor correlation between the stacking and flexibility.

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Figures

FIGURE 1
FIGURE 1
Diagonal force constants in basepair step harmonic deformation potentials obtained from molecular dynamics simulations (solid line) as compared with those from the x-ray study of Olson et al. (1998) (dotted line). Error bars in the simulation data indicate the range of values observed. These constants describe the energetics of a deformation in which only one helicoidal parameter is changed whereas the others retain their equilibrium values. See Table 1 for a complete list of all constants, including the coupling terms.
FIGURE 2
FIGURE 2
Comparison of the relative importance of various coupling terms. The values indicate the relative error caused by neglecting the coupling term in a deformation where only two different variables are involved. See text for details. (a) Results from simulations. (b) Crystallographic data from Olson et al. (1998). In simulations, the other couplings not shown in the figures form a narrow belt near the zero value; in crystallographic data, however, they uniformly fill the space between zero and the uppermost curves.
FIGURE 3
FIGURE 3
Correlation coefficients describing pairwise correlations of fluctuations of helicoidal parameters in different basepairs along a sequence. The numbers on the x axis indicate the distance between the basepairs. Thus, the value at x = 0 expresses a correlation of movements of a basepair with itself; it is 1 by definition and is not shown in the figure. The value at x = 1 is a correlation coefficient for the nearest-neighboring basepair steps, x = 2 indicates the next-nearest neighbors, etc. The data are averages over all equidistant steps in both simulated sequences. Note that most of the correlations fade away beyond the nearest neighbor; however, slide and twist persist to a longer distance, and roll is almost uncorrelated.
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