Ramachandran-like Conformational Space for DNA

DNA’s\nability to exist in a wide variety of structural forms,\nsubforms, and secondary motifs is fundamental to numerous biological\nprocesses and has driven the development of biotechnological applications.\nMajor determinants of DNA flexibility are the multiple torsional degrees\nof freedom around the phosphodiester backbone. This high complexity\ncan be rationalized by using two pseudotorsional angles linking atoms\nP and C4′, from which Ramachandran-like plots can be built.\nIn this contribution, we explore the distribution of η (eta:\nC4′<sub>i–1</sub>-P<sub>i</sub>-C4′<sub>i</sub>-P<sub>i+1</sub>) and θ (theta: P<sub>i</sub>-C4′<sub>i</sub>-P<sub>i+1</sub>-C4′<sub>i+1</sub>) angles in known\nexperimental structures retrieved from the Protein Data Bank (PDB),\nsubdividing the conformational space into different datasets. After\nthe removal of the canonical/helical conformations typical of the\nB-form, we find the existence of a conformational map with clearly\npermitted and forbidden regions. Some of these regions are populated\nwith specific DNA forms, like Z- or A-DNA, or by specific secondary\nmotifs, like G-quadruplexes and junctions. We evaluated the sequence\ndependency and energy relationship among the high-density regions\nidentified in the η–θ space. Furthermore, we analyzed\nthe effect produced by proteins and cations when bound to DNA, finding\nthat specific proteins produce some nonhelical conformations, while\nother regions appear to be stabilized by divalent cations.