None of the current force fields is perfect and many problems persist in DNA and RNA simulations.

The canonical DNA double helix is described relatively well, although the equilibria between the BI/BII backbone substates and the A-DNA and B-DNA forms may still be inaccurate. While the ZI substate of Z-DNA is described relatively well by OL15 and OL21, the population of the ZII substate is likely underpredicted. Importantly, some non-native α/γ backbone substates are strongly populated in antiparallel guanine DNA quadruplex with OL15. Non-canonical α/γ were overpopulated in Z-DNA with OL15, which was partially ameliorated by OL21.

Yet more problems may be found in RNA, where only a few of the existing loop structures are described correctly and many non-canonical motifs, such as GpU platform in sarcin/ricin loop (SRL) do not behave well in MD simulations.

It is likely that not all of the known shortcomings can be overcome using a simplified, pairwise-additive potential function. Nevertheless, force fields for nucleic acids are under constant development and further improvements can be expected.

Feedback on the performance of our force fields and especially pointing us to new difficult cases is greatly appreciated.