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