High-Pressure Single-Molecule Studies on Non-canonical Nucleic Acids and Their Interactions

Abstract

High hydrostatic pressure affects the structure, dynamics, and the stability of biomolecular systems. Therefore, in order to describe the entire energy and conformational landscape and the set of parameters required for a comprehensive understanding of the general phase behavior of biomolecular systems, one needs to scan the full thermodynamic parameter space, including high pressure. In addition, high hydrostatic pressures are encountered in organisms living in the deep sea and in subseafloor ecosystems, which constitute a significant portion of the Earth’s biosphere and where pressures up to the 1000 bar level or more prevail. High pressure is also a key parameter in the context of exploring the origin and the physical limits of life on Earth or on other planets and moons. In this review, we lay out the conceptual framework for exploring conformational fluctuations, dynamical properties, and the activity of biomolecular systems using pressure perturbation, focusing in particular on non-canonical nucleic acid systems, such as DNA hairpins, G-quadruplexes and i-motifs, and their interactions. Moreover, the effects of cosolutes (salts, osmolytes), macromolecular crowding, and intrinsically disordered peptides on the conformational dynamics of non-canonical nucleic acid structures at ambient and high-pressure conditions will be discussed.