Ramachandran-like Conformational Space for DNA

Abstract

DNA’s ability to exist in a wide variety of structural forms, subforms, and secondary motifs is fundamental to numerous biological processes and has driven the development of biotechnological applications. Major determinants of DNA flexibility are the multiple torsional degrees of freedom around the phosphodiester backbone. This high complexity can be rationalized by using two pseudotorsional angles linking atoms P and C4′, from which Ramachandran-like plots can be built. In this contribution, we explore the distribution of η (eta: C4′_i–1-P_i-C4′_i-P_i+1) and θ (theta: P_i-C4′_i-P_i+1-C4′_i+1) angles in known experimental structures retrieved from the Protein Data Bank (PDB), subdividing the conformational space into different datasets. After the removal of the canonical/helical conformations typical of the B-form, we find the existence of a conformational map with clearly permitted and forbidden regions. Some of these regions are populated with specific DNA forms, like Z- or A-DNA, or by specific secondary motifs, like G-quadruplexes and junctions. We evaluated the sequence dependency and energy relationship among the high-density regions identified in the η–θ space. Furthermore, we analyzed the effect produced by proteins and cations when bound to DNA, finding that specific proteins produce some nonhelical conformations, while other regions appear to be stabilized by divalent cations.