Thermodynamic properties of water molecules in the presence of cosolute depend on DNA structure: a study using grid inhomogeneous solvation theory

Miki Nakano,Osamu Miyashita,Shigenori Tanaka,Naoki Sugimoto,Florence Tama,Shu-Ichi Nakano,Hisae Tateishi-Karimata

doi:10.1093/nar/gkv1133

Abstract

In conditions that mimic those of the living cell, where various biomolecules and other components are present, DNA strands can adopt many structures in addition to the canonical B-form duplex. Previous studies in the presence of cosolutes that induce molecular crowding showed that thermal stabilities of DNA structures are associated with the properties of the water molecules around the DNAs. To understand how cosolutes, such as ethylene glycol, affect the thermal stability of DNA structures, we investigated the thermodynamic properties of water molecules around a hairpin duplex and a G-quadruplex using grid inhomogeneous solvation theory (GIST) with or without cosolutes. Our analysis indicated that (i) cosolutes increased the free energy of water molecules around DNA by disrupting water–water interactions, (ii) ethylene glycol more effectively disrupted water–water interactions around Watson–Crick base pairs than those around G-quartets or non-paired bases, (iii) due to the negative electrostatic potential there was a thicker hydration shell around G-quartets than around Watson–Crick-paired bases. Our findings suggest that the thermal stability of the hydration shell around DNAs is one factor that affects the thermal stabilities of DNA structures under the crowding conditions.

Highlights

Depending on sequence and solution conditions, nucleic acids can adopt triplex, i-motif and G-quadruplex structures in addition to the canonical B-form duplex composed of Watson–Crick base pairs [1,2,3,4]
As the first step to investigate the effects of environment on the thermal stabilities of DNA structures, we focused on the thermodynamic properties of water molecules around DNA, it is expected that the interaction between cosolutes and DNA is important
These results indicate that the differences in density profiles around structured HP and thrombin binding aptamer (TBA) were caused by the difference in DNA structures rather than the difference of DNA sequences

Summary

Introduction

Depending on sequence and solution conditions, nucleic acids can adopt triplex, i-motif and G-quadruplex structures in addition to the canonical B-form duplex composed of Watson–Crick base pairs [1,2,3,4]. Age-related diseases and premature aging syndromes are characterized by short telomeres, which form G-quadruplex in vivo [8,9,10,11]. Some proteins, such as the tumor suppressor protein p53 and Human DNA polymerase-L, have evolved to recognize certain Watson–Crick or Hoogsteen base pairs [12,13,14]. To understand physiology and metabolism in vivo, it is necessary to understand the principles that govern thermal stability of nucleic acid structures in conditions that mimic those of living cells

Methods

Results

Conclusion