Static and animated molecular views of a tumorigenic chemical bound to DNA

Conference · Tue Jan 01 00:00:00 EST 1991

OSTI ID:5476622

Broyde, S; Xu, Rong ^[1]; Hingerty, B E ^[2]; O'Handley, S F; Krugh, T R ^[3]

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1. New York Univ., NY (USA)
2. Oak Ridge National Lab., TN (USA)
3. Rochester Univ., NY (USA). Dept. of Chemistry

Static and dynamic molecular views of a short segment of DNA modified by the tumorigenic aromatic amine 2-acetylaminofluorene (AAF) have been realized by a combination of high resolution nuclear magnetic resonance (NMR) studies in solution and molecular mechanics and molecular dynamics simulations carried out on supercomputers. Thus, the effect of AAF on the structure of the Watson-Crick B-DNA double helix has been elucidated, after two decades of intense interest, via a powerful synergy between state-of-the-art supercomputing NMR investigations. The AAF is situated in the minor groove of a B-DNA double helix which flexes and bends, and the carcinogen moves between positions where it is stacked with adjacent DNA base and positions where it protrudes further into the groove. The AAF modified DNA base, guanine, is displaced from its normal situation paired with partner cytosine. Also, a base pair adjacent to the modification becomes more mobile. These molecular views offer some possible insight on the early molecular events that may implicate AAF in tumor initiation. 16 refs., 3 figs.

• Research Organization: Oak Ridge National Lab., TN (United States)
• Sponsoring Organization: USDOE; NIEHS; National Science Foundation (NSF); USDOE, Washington, DC (United States); National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); National Science Foundation, Washington, DC (United States)
• DOE Contract Number: FG02-90ER60931; AC05-84OR21400
• OSTI ID: 5476622
• Report Number(s): CONF-9105202-6; ON: DE91015303
• Resource Relation: Conference: Power supercomputer users meeting, Gaithersburg, MD (United States), 21-22 May 1991
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ACETYLAMINOFLUORENES
BIOLOGICAL EFFECTS
DNA
DYNAMICS
DNA ADDUCTS
MOLECULAR STRUCTURE
COMPUTERIZED SIMULATION
A CODES
BIOCHEMISTRY
COMPUTER GRAPHICS
D CODES
DNA BASE TRANSITIONS
DNA SEQUENCING
MOLECULAR BIOLOGY
MUTAGENESIS
NUCLEAR MAGNETIC RESONANCE
SUPERCOMPUTERS
THREE-DIMENSIONAL CALCULATIONS
ADDUCTS
CHEMISTRY
COMPUTER CODES
COMPUTERS
DIGITAL COMPUTERS
MAGNETIC RESONANCE
MECHANICS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RESONANCE
SIMULATION
STRUCTURAL CHEMICAL ANALYSIS
550200* - Biochemistry