Structure-function studies of DNA damage using ab Initio quantum mechanics and molecular dynamics simulation

Conference · Sat Dec 31 00:00:00 EST 1994

OSTI ID:134839

Miller, J; Miaskiewicz, K ^[1]; Osman, R ^[2]

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1. Pacific Northwest Lab., Richland, WA (United States)
2. City Univ. of New York, NY (United States)

Studies of ring-saturated pyrimidine base lesions are used to illustrate an integrated modeling approach that combines quantum-chemical calculations with molecular dynamics simulation. Electronic structure calculations on the lesions in isolation reveal strong conformational preferences due to interactions between equatorial substituents to the pyrimidine ring. Large distortions of DNA should result when these interactions force the methyl group of thymine to assume an axial orientation, as is the case for thymine glycol but not for dihydrothymine. Molecular dynamics simulations of the dodecamer d(CGCGAATTCGCG){sub 2} with and without a ring-saturated thymine lesion at position T7 support this conclusion. Implications of these studies for recognition of thymine lesions by endonuclease III are also discussed.

• Research Organization: New York Academy of Sciences, New York, NY (United States)
• DOE Contract Number: AC06-76RL01830; FG02-88ER60675
• OSTI ID: 134839
• Report Number(s): CONF-9307221-; TRN: 95:007741-0005
• Resource Relation: Conference: DNA damage: effects on DNA structure and protein recognition, Burlington, VT (United States), 31 Jul - 4 Aug 1993; Other Information: PBD: 1994; Related Information: Is Part Of DNA damage: Effects on DNA structure and protein recognition; Wallace, S.S.; Van Houten, B.; Kow, Yoke Wah [eds.]; PB: 395 p.
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 MATHEMATICS
COMPUTERS
INFORMATION SCIENCE
MANAGEMENT
LAW
MISCELLANEOUS
DNA
STRUCTURE-ACTIVITY RELATIONSHIPS
MUTATIONS
STRAND BREAKS
GENETIC RADIATION EFFECTS
CONFORMATIONAL CHANGES
DYNAMICS
COMPUTERIZED SIMULATION
THYMINE
ORIENTATION
PYRIMIDINES
ENDONUCLEASES
ENZYME ACTIVITY
PROTEINS
NUCLEOTIDES
QUANTUM MECHANICS
ULTRAVIOLET RADIATION
IONIZING RADIATIONS
ESCHERICHIA COLI
DNA REPAIR