Unusual Nucleic Acid Structures: G-DNA, i-DNA and A-zipper. Insights from Large-scale Molecular Dynamics Simulations
State of the art explicit solvent MD simulations has provided a unique new insight into the molecular interactions in unusual nucleic acids [1-4]. Four stranded DNA assemblies, i-DNA and G-DNA, are exceptionally rigid molecules with unique mechanical properties and molecular interactions. i-DNA differs from all nucleic acid forms in that it has a repulsive intrinsic stacking due to hemiprotonation of the cytosine base pairs in its stem . The simulations also demonstrate a key role of monovalent cations in stabilization of G-DNA molecules . The number of cations in the channel can be reduced without destabilization of the structure and this allows a smooth exchange of the cations with a solvent. A complete removal of cations leads to marked destabilization of the quadruplex. Alternative very stable conformations of the native G-DNA stem with shifted strands have been identified and suggested to participate in last stages of the formation of the stem . Analysis of the A-zipper duplex revealed a novel local conformational variation stabilized by a concerted interplay of several contributions: re-puckering, stacking adjustment, highly ordered hydration sites with exceptionally long-residing solvent molecules, phosphate clustering, and specific monovalent sodium cation coordination . The behavior of loop regions of G-DNA molecules were studied in detail, especially their function in mechanism of ion exchange between the ion channel and the solvent [2,4].
Results of molecular dynamics simulations of these molecules show an excellent agreement between theoretical and experimental structures while providing numerous novel insights. MD studies represent an indispensable contribution to better understanding of structure and dynamics of these biologically interesting molecules. We have carried out more than 150 ns of simulations on the unusual DNA forms, making out project the most extensive MD study ever reported on nucleic acids.
1. N. Spackova, I. Berger, M. Egli, J. Sponer : J. Am. Chem. Soc. 120, 1998, 6147-6151.
Nada Spackova1, Imre Berger2, and Jiri Sponer3
1Institute of Biophysics, Academy of Sciences of the Czech Republic,