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: Recent work by Dans et al. (28) on the polymorphism of the CG step observed that BII states in the GR step of a CGR trinucleotide are associated with the formation of a C8-H…O3′ hydrogen bond between the C8-H group of the R base and the O3′ atom of the corresponding 5′-phosphate group. We can now extend the Dans et al. (28) analysis to the full set of sequences in the ABC microsecond trajectories. Inspecting the time series and the overall distribution of C8…O3′ distances shows that a 4-Å cutoff is appropriate to separate bonded and unbonded states. The resulting tetranucleotide-dependent occupancies for the central C8-H…O3′ hydrogen-bonded state (which cannot arise for central RY steps) are summarized in Figure 6. For central RR steps, there is a perfect correlation between the occupancies of the hydrogen-bonded state (Figure 6) and the BII state (Figure 5) for all tetranucleotide contexts. An almost identical correlation is observed for YR steps. A more detailed analysis of the associated time series shows that, averaging over all cases with central RR and YR dinucleotides, BII conformations are associated with backbone hydrogen bonds in 90% of the snapshots and, conversely, backbone hydrogen bonds are associated with BII conformations in 87% of snapshots. This very high correlation holds for both high (generally central RR) and low (generally central YR) BII occupancy steps.
Affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.