MD Simulation of DNA Oligonucleotides Containing Base Damage (fsd4)
EMSL Project ID
2303
Abstract
Objectiive:This pilot project will investigate the performance of NWChem for simulating the molecular dynamics of double-strand DNA when one of the base pairs in a dodecamer (approximately one turn of a double helix) contains a covalent chemical modification. Approach: Starting structures for MD simulation will be developed from standard B-DNA. A guanine base near the center of the dodecamer will be changed to 8oxo-guanine by addition of an oxygen atom at C8 and a hydrogen atom at N7 to give the 6,8-diketo tautomer. 22 Na+ counterions will be added to obtain a neural solute. DNA and counterions will be placed in a large box of water molecules to approximate solvation. The Particle-Mesh-Ewald method will be used to calculate long-range electrostatic interactions. Nanosecond-long simulations will be carried out with 8oxo-guaine in different molecular environments. Simulations will be started with 8oxo-guanine forming a Watson-Crick base pair with cytosine and with 8oxo-guanine in an extrahelical configuration. These results will be compared with a simulation having a normal GC base pair at the damage site. We will also investigate this case where 8oxo-guanine forms a Hoogsteen base pair with adenine. DNA curves, Dials & Windows and NWchem will be used to analyze these simulation results. Free-energy changes when 8oxo-guanine in a base pair with either cytosine or adenine is rotated into an extrahelical configuration will be calculated by thermodynamic integration.
Project Details
Project type
Exploratory Research
Start Date
2001-08-03
End Date
2001-10-01
Status
Closed
Released Data Link
Team
Principal Investigator
Related Publications
Engelmann MD, LA Metz, JE Delmore, MH Engelhard, and NE Ballou. 2008. "Electrodeposition of Technetium on Platinum for Thermal Ionization Mass Spectrometry (TIMS)." Journal of Radioanalytical and Nuclear Chemistry 276(2):493-498. doi:10.1007/s10967-008-0532-y