Structure-function studies of DNA damage using AB INITIO quantum mechanics and molecular dynamics simulation
- Pacific Northwest Lab., Richland, WA (United States)
- Mount Sinai School of Medicine, New York, NY (United States). Dept. of Physiology and Biophysics
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:
- Pacific Northwest Lab., Richland, WA (United States); Mount Sinai School of Medicine, New York, NY (United States). Dept. of Physiology and Biophysics
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- AC06-76RL01830; FG02-88ER60675
- OSTI ID:
- 10108409
- Report Number(s):
- PNL-SA-22964; CONF-9307160-1; ON: DE94004285
- Resource Relation:
- Conference: New York Academy of Sciences conference on DNA damage: effects on DNA structure and protein recognition,Burlington, VT (United States),31 Jul - 4 Aug 1993; Other Information: PBD: [1993]
- Country of Publication:
- United States
- Language:
- English
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