Heterogeneous hydration patterns of G-quadruplex DNA

Abstract

G-quadruplexes (GQs) are guanine-rich, non-canonical nucleic acid structures that play fundamental roles in biological processes. Their structure and function are strongly influenced by their hydration shells. Although extensively studied through various experimental and computational methods, hydration patterns near DNA remain under debate due to the chemically and topologically heterogeneous nature of the exposed surface. In this work, we employed all-atom molecular dynamics (MD) simulation to study the hydration patterns of GQ DNA. The Drude oscillator model was used in MD simulation as a computationally efficient method for modeling electronic polarization in DNA ion solutions. Hydration structure was analyzed in terms of radial distribution functions and high-density three-dimensional hydration sites. Analysis of hydration dynamics focused on self-diffusion rates and orientation time correlation at different structural regions of GQ DNA. The results show highly heterogeneous hydration patterns in both structure and dynamics; for example, there are several insular high-density sites in the inner channel, and ‘spine of water’ in the groove. For water inside the loop, anomalous diffusion is present over a long time scale, but for water around the phosphate group and groove, diffusion becomes normal after ∼ 30 ps. These essentially correspond to deeply buried structural water and strong interaction with DNA, respectively.

On Water Arrangements in Right- and Left-Handed DNA Structures

“…This is the case whether G4 sequences are found in promoter or telomere regions, or in 5′/3′-UTR sequences. The importance of hydration in maintaining G-quadruplex structural integrity has been highlighted in several studies [ 46 , 47 , 48 , 49 ]. The hydration of high-resolution RH DNA G4s has been analyzed [ 50 ], and patterns of extended spines of groove waters have been observed in a groove of an antiparallel G4 structure, analogous to but distinct from the RH spine found in duplex B-DNAs.…”