Artificial analogues of the natural nucleic acids have attracted interest as a diverse class of information storage molecules capable of self-replication. In this study, we use the computational potential energy landscape framework to investigate the structural and dynamical properties of xylo- and deoxyxylo-nucleic acids (XyNA and dXyNA), which are derived from their respective RNA and DNA analogues by inversion of a single chiral center in the sugar moiety of the nucleotides. For an octameric XyNA sequence and the analogue dXyNA, we observe facile conformational transitions between a left-handed helix, which is the free energy global minimum, and a ladder-type structure with approximately zero helicity. The competing ensembles are better separated in the dXyNA, making it a more suitable candidate for a molecular switch, whereas the XyNA exhibits additional flexibility. Both energy landscapes exhibit greater frustration than we observe in RNA or DNA, in agreement with the higher degree of optimization expected from the principle of minimal frustration in evolved biomolecules.