Exploring potentially alternative non-canonical DNA duplex structures through simulation

Hopkins proposed an alternative and chirally distinct family of double-stranded DNA (dsDNA) models that have antiparallel chains with 5'→3' senses opposite to those of the right-handed Watson-Crick (WC) family. Termed configuration II, this family of dsDNA models contains both right-handed (II-R) and left-handed (II-L) forms, with Z-DNA as an example of the latter. Relative interstrand binding energies for six DNA duplex models, two each of configuration I-R (standard WC canonical B-DNA), II-R, and II-L for the duplex d(CGCGAATTCGCG), have been estimated under identical conditions using MM-PBSA analysis from molecular dynamics trajectories using three different AMBER force fields. These simulations support the stereo chemical soundness of configuration II dsDNA forms. Recent force fields (Barcelona Supercomputing Center [BSC] [bsc1] and Olomouc 2015 [OL15]) successfully render stable II-L structures, whereas the previous force field, bsc0, generated stable II-R structures, although with an energy difference between II-R and II-L of ∼30 kcal/mol. Communicated by Ramaswamy H. Sarma.