A Minimal Model of B-DNA

Recently it has been found that stable and accurate molecular dynamics (MD) of B-DNA duplexes can be obtained in relatively inexpensive computational conditions with the bulk solvent represented implicitly, but the minor groove filled with explicit water (J. Am. Chem. Soc. 1998, 120, 10928). The present paper further explores these simulation conditions in order to understand the main factors responsible for the observed surprisingly good agreement with experimental data. It appears that in the case of the EcoRI dodecamer certain sequence specific hydration patterns in the minor groove earlier known from experimental data are formed spontaneously in the course of MD simulations. The effect is reliably reproduced in several independent computational experiments in different simulation conditions. With all major groove water removed, closely similar results are obtained, with even better reproducibility. On the other hand, without explicit hydration, metastable dynamics around a B-DNA like state can be obtained which, however, only poorly compares with experimental data. It appears, therefore, that a right-handed DNA helix with explicitly hydrated minor groove is a minimal model system where the experimental properties of BDNA can be reproduced with non-trivial sequence-dependent effects. Its small size makes possible virtually exhaustive sampling, which is a major advantage with respect to alternative approaches. An appendix is included with a correction to the implicit leapfrog integrator used in internal coordinate MD.