Hydration of DNA in aqueous solution: NMR evidence for a kinetic destabilization of the minor groove hydration of d-(TTAA)₂versus d-(AATT)₂segments

Abstract

The residence times of the hydration water molecules near the base protons of d-(GTGGAATTCCAC)2 and d-(GTGGTTAACCAC)2 were investigated by nuclear magnetic resonance (NMR) spectroscopy. Nuclear Overhauser effects (NOE) were observed between base protons of the DNA and hydration water in NOESY and ROESY experiments. Large positive NOESY cross peaks observed between the resonances of the water and the adenine 2H protons of the central d-(AATT)2 segment in the duplex d-(GTGGAATTCCAC)2 indicate the presence of a 'spine of hydration' with water molecules exhibiting residence times on the DNA longer than 1 nanosecond. In contrast, no positive intermolecular NOESY cross peaks were detected in the d-(TTAA)2 segment of the duplex d-(GTGGTTAACCAC)2, indicating that no water molecules bound with similarly long residence times occur in the minor groove of this fragment. These results can be correlated with the larger width of the minor groove in d-(TTAA)2 segments as compared to that in d-(AATT)2 segments, as observed previously in single crystal structures of related oligonucleotide duplexes in B type conformation. The present experiments confirm earlier experimental results from single crystal studies and theoretical predictions that a 5'-dTA-3' step in the nucleotide sequence interrupts the spine of hydration in the minor groove.

Molecular dynamics simulation study of DNA dodecamer d(CGCGAATTCGCG) in solution: conformation and hydration

“…Particularly, the network in the Dickerson dodecamer forms a spinelike structure that spans the entire A:T-rich region Kopka et al, 1983). Since then, extensive studies, using a wide variety of biophysical methods, including X-ray crystallography Drew et al, 1982;Kipka et al, 1983;Neidle et al, 1980), NMR (Liepinsh et al, 1994) and Raman spectroscopy (Tao, 1993), have been devoted to this interesting structure because of its underlying relation to sequence dependent deformation as well as to sequence speci®city.…”

DNA Minor Groove Binders: an Overview on Molecular Modeling and QSAR Approaches

“…Investigations on series of naphthylquinolines, suitably functionalised with additional structural features of the side chain, such as LS-08 (37) and MHQ-12 (38), also demonstrated the alkylamine substituent fits snugly into the minor groove of the triplex, providing additional stabilizing interactions, It is known from a large number of experimental studies that the minor groove in AATT sequences is narrow on average with a well-ordered hydration matrix, whereas with TTAA the groove is wider with a more disordered hydration structure [84,85]. Differences in group positioning and stacking energetics lead to these structural and hydration differences [86][87][88] which can be mirrored by molecular dynamics calculations.…”

An NMR Study of d(CTACTGCTTTAG).d(CTAAAGCAGTAG) Showing Hydration Water Molecules in the Minor Groove of a TpA Step

“…Positive or negative NOESY cross-peaks are observed if the residence time of water molecules near DNA protons is respectively longer or shorter than, approximately, SOO ps; ROESY crosspeaks are always negative. Cross-peaks due to proton exchange between the water and the DNA have positive signs both in NOESY and in ROESY ( 18,27).…”

“…Most of the present NMR results are based on the analysis of: I) chemical shifts of the adenine and thymine protons; 2) the adenine H2 and H8 line widths (24)(25)(26); 3) the minor groove width from, particularly, NOEs related to H2(n)-H I '(m+ I) distances; and 4) water molecule residence times derived from the signs of NOEs between the water signal and the DNA signals in NOESY and ROESY spectra (18,20,27).…”