Molecular dynamics of minimal B‐DNA

Abstract

Stable and accurate molecular dynamics (MD) of B-DNA duplexes can be obtained in inexpensive computational conditions where only the minor groove is filled with water while the bulk solvent is represented implicitly. This model system presents significant theoretical as well as practical interest because, due to its simplicity and exceptional computational performance, it can be employed in simulations of very long DNA fragments. To better understand its properties and clarify the physical background of the effects produced by the limited water shell, dynamics of several different DNA oligomers was studied. It is found that optimal simulation conditions are reached when the explicit water is confined within the minor groove while the major groove is cleaned periodically. The internal solvent mobility appears high enough to observe in the nanosecond time scale spontaneous formation of sequence-specific hydration patterns known from experiments. It is shown that the model produces stable MD trajectories close to the B-DNA form regardless of the base pair sequence and that, on the other hand, the dynamics are strongly sequence dependent. Independent observations suggest that B-DNA with only minor groove hydrated resembles its natural thermodynamic state at low water concentration; therefore, this model system can be tentatively called “minimal B-DNA.” © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 457–467, 2001