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: The conclusions of our analysis are summarized in Figure 4 and can be compared with the results of Dans et al. (14) in Supplementary Figure S6. The results are: (i) strongly non-Gaussian distributions do not arise at all in RY steps, and are restricted to shift for GG steps, slide for all RR steps, and twist for all RR and YR steps. The other three inter-BP, as well as all intra-BP, parameters do not significantly deviate from Gaussian behavior in any sequence context; (ii) only GG slide and CG twist show clear multiple peaks. We remark that while our analysis has identified tetranucleotide fragments whose central base pair steps interconvert between multiple conformational substates, it certainly does not rule out the possibility that other fragments can also have multiple substates, but with populations that are difficult to distinguish using only helical parameter distributions.
Affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.