Abstract
We present the results of microsecond molecular dynamics simulations carried out by the ABC group of laboratories on a set of B-DNA oligomers containing the 136 distinct tetranucleotide base sequences. 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. Beyond sequence effects on average helical parameters and conformational fluctuations, we also identify tetranucleotide sequences that oscillate between several distinct conformational substates. 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.
Highlights
Once the first single crystal structure of a DNA oligomer was obtained [1,2], it became clear that base sequence could have a significant impact on structure, even within a single conformational family, such as B-DNA
The results discussed in this article are based on molecular dynamics trajectories for 39 double-stranded B-DNA oligomers, each containing 18 base pairs
The differences between the average parameters vary between oligomers, but even in the worst cases are within 0.25 Afor translational helical parameters, within 2◦ for rotational helical parameters, and within 5◦ for backbone dihedrals and sugar puckers and, in most cases, they are less than half these values
Summary
Once the first single crystal structure of a DNA oligomer was obtained [1,2], it became clear that base sequence could have a significant impact on structure, even within a single conformational family, such as B-DNA. Sequence-dependent conformational variations can be expected to play a significant role in how proteins interact with the double helix, and notably in determining how binding proteins recognize their target sites [3,4,5,6,7]. Such ‘indirect recognition’ processes have been confirmed in a wide variety of protein–DNA interactions.
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