Solution structure of nucleic acids by nuclear magnetic resonance (NMR) spectroscopy

Miscellaneous · Wed Jan 01 00:00:00 EST 1992

OSTI ID:7044308

Cheng, J W

Evidence that dehydration effects and crystal packing effects can alter the global and local structure of nucleic acids in the crystalline state has led to attempts to determine their structure directly in solution. Parameterization of the non-bonded force fields for theoretical methods such as energy minimization and molecular dynamics calculations is incomplete and NMR spectroscopy appears to be the most promising spectroscopic approach to determining nucleic acid solution structure. The nuclear Overhauser effect (NOE), the dipole-dipole interaction between proton pairs, serves as the major tool in NMR structural studies. This, along with vicinal proton scalar coupling, can be used in generating and refining structural coordinates. The polynucleotide backbone can be constrained quite well purely from NMR data. These approaches were applied to a (Py-Pu)[sub n] duplex, which exhibits alternating base pair structure, and DNA duplexes containing adjacent GA Mismatches were found to depend entirely on the neighboring base pairs. A cross-strand base stacking pattern with sheared G:A pairing and a high energy B[sub II] phosphate backbone conformation was reported. Oligo-dA[sub n] tracts undergo a smooth structural transition from a B conformation at the 5[prime] end to a B[prime] conformation at the 3[prime] end. This narrowing of the minor groove from ca. 12[angstrom] to 8--9[angstrom] is readily detectable from the progressively increasing cross-strand AH2-H1[prime] NOEs. The solution structure of the DNA sequence [d(CGTAAATTTACG)[sub 2]] containing the A[sub 3]T[sub 3] sequence was determined using NMR and distance geometry methods. The structure contains flanking B-DNA with a narrowing minor groove and B[prime]-DNA at the center of this A[sub 3]T[sub 3] sequence. The solution conformation of an RNA duplex with U[center dot]U mismatches was studied by NMR and molecular modeling. Preliminary studies on triple-stranded nucleic acids by NMR are described.

• Research Organization: Washington Univ., Seattle, WA (United States)
• OSTI ID: 7044308
• Resource Relation: Other Information: Thesis (Ph.D.)
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
NUCLEIC ACIDS
NUCLEAR MAGNETIC RESONANCE
STRUCTURAL CHEMICAL ANALYSIS
DNA
MOLECULAR STRUCTURE
RNA
SOLUTIONS
DISPERSIONS
MAGNETIC RESONANCE
MIXTURES
ORGANIC COMPOUNDS
RESONANCE
400201* - Chemical & Physicochemical Properties
550200 - Biochemistry