MOLECULAR-DYNAMICS SIMULATIONS SUGGEST THAT THE ECO RI KINK IS AN EXAMPLE OF MOLECULAR STRAIN

The energy surface in the vicinity of the ''Eco RI kink'' was investigated by conducting both in vacuo molecular dynamics simulations as well as a simulation with explicit solvent. The in vacuo simulations used the ''all atom'' AMBER 3.0 force field with a distant dependent dielectric function and ''hydrated'' counter ions while the simulation with explicit solvent used the AMBER 4.0 force field, fully charged phosphates and counter ions and a dielectric constant of 1.0.. The thrust of the simulations was to discriminate between two models of the energy surface of the deformed DNA as found in the recognition complex with Eco RI endonuclease. In the intrinsic model, the kinked DNA is a local minimum of the energy surface intrinsic to the DNA itself while in the strained model there is no significant energy barrier separating kinked and regular B-DNA. The two models have significant implications for theories of indirect recognition of DNA based on sequence-dependent deformability. The simulations suggest that the Eco RI-kinked structure is an example of molecular strain because it is not near a minimum of any of the potential energy functions examined. The simulations leave the question of an energy barrier somewhat open and raise the possibility that the Eco RI kink is at (or near) a point of dynamic instability of the energy surface (either a true maximum or a saddle point).