Smallest realistic model of the phosphodiester linkage Contains hydrophobic, polar, and ionic solvation sites

The conformational flexibility of molecules often plays a key role in the properties of biological systems. In particular, the flexibility of dimethyl phosphate (DMP) is central to a number of important systems, including nucleic acids and phospholipids.

Figure 1. The a) gauche-gauche and b) gauche-trans conformers of dimethyl phosphate.

The energetics of various conformers of DMP has been studied with first principles electronic structure methods, which indicate that the gauche-gauche and gauche-trans conformers (shown in Fig. 1) are the most stable in the gas-phase, with the gauche-gauche conformer being slightly lower in energy. However, recent calculations on the monohydrate form of DMP have indicated that the gauche-trans conformer may be preferentially stabilized, relative to the gauche-gauche conformer, as DMP is solvated by individual water molecules.

Figure 2. The evolution of the C1-O3-O4-C2 torsion angle, and b) the distance between the sodium cation and the O1 and O2 atoms in the gauche-gauche simulation.

In order to have a more complete understanding of the influence of an aqueous environment on DMP, we have performed first principles molecular dynamics simulations on the dimethyl phosphate anion along with a sodium counterion in water. Interestingly, we find that in the simulation of the gauche-gauche form, DMP undergoes an abrupt change in conformation to gauche-trans midway through the simulation. Closer inspection of the simulation data revels that this change in conformation appears to be mediated by the approach of the sodium cation to one of the anionic oxygen atoms of the DMP (see Fig. 2). This is in contrast to previous studies on gas phase complexes, which find that the presence of the sodium cation should have little or no effect on the dynamical properties of DMP.

UCRL-MI-
Date last modified: 9/27/00
Contact Miriam Rinnert for website information