μABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA.
Bottom Line: We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature.We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step.By analyzing the conformation of the phosphodiester backbones, it is possible to understand for which sequences these substates will arise, and what impact they will have on specific helical parameters.
Affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.Show MeSH
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Mentions: Figure 3 shows 11 cases of helical parameter distributions that were identified as having significant deviations from Gaussian behavior. Each panel illustrates the distributions of a given helical parameter for all possible flanking sequences of a given dinucleotide step. The 11 panels display all cases for which at least half of the flanking sequence contexts lead to asymmetric distributions, shoulders or multiple peaks. Comparing the different curves within a single panel confirms that the flanking base pairs have a strong effect on the central base pair step parameter distributions. The most extreme example is that of CG twist which suggests that there are at least two wells, one centered at around 20° and the other around 40°. Figure 3 shows that while all CG twist distributions sample both wells, the relative population of the two states is strongly affected by the flanking sequence. In particular Y..R flanking sequences (plotted in blue) lead CG steps to prefer low-twist values, while R..Y flanking sequences (green) favor high twists, and R..R sequences (red) leave the CG step free to sample both states with more uniform frequencies (see also (28)). Similar behaviors can be observed in the other panels of Figure 3 for the twist, shift and slide distributions of the other indicated central dinucleotide steps.
Affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.