Book of Abstracts: Albany 2003
June 17-21 2003
Studying Ion Distributions Around DNA
As a highly charged polyelectrolyte, it is clear that double helical DNA will be extremely sensitive to its solvent and counterion environment. Ion distributions around DNA and their impact on its structural and dynamic properties have therefore been a topic of interest for many years.
Molecular dynamics simulations are an ideal tool for studying such properties in atomic detail, however, until recently, limitations in computer power, the quality of force fields and also the treatment of long range electrostatics, have hindered such investigations. Compared to most conformational fluctuations of the double helix, ion movements are rather slow and consequently it is necessary to carry out very long (and stable) simulations in order to obtain statistically reliable results.
We will present the results of a 35 ns simulation on a B-DNA duplex, d(CCATGCGCTGAC). This sequence contains a binding site for MHha I methyltransferase and has already been the subject of a molecular dynamics study of base flipping involved in the activity of this enzyme (1).
The present study is carried out using AMBER 6.0 with the parm99 force field. The simulation is performed using periodic boundary conditions in a truncated octahedral box containing roughly 5000 TIP3P water molecules. Electrostatic interactions are treated using particle mesh Ewald summations. The DNA duplex is neutralized with 22 sodium ions, whose behavior during the dynamics is analyzed using system configurations stored every ps.
The results show that more than 30 ns of simulation are necessary before the ions have completely visited the solvent space surrounding the DNA duplex. This time is also sufficient for all ions to have visited the DNA grooves at least once. By analyzing the trajectories of each ion we have been able to identify favorable ion binding sites, to define ion residence times and to look for correlations between ion displacements in and out of the grooves of the double helix and its corresponding conformational fluctuations.
Laboratoire de Biochimie Théorique