Refinenement of the AMBER force field for nucleic acids:: Improving the description of α/γ conformers

We present here the parmbsc0 force field, a refinement of the AMBER parm99 force field, where emphasis has been made on the correct representation of the alpha/gamma concerted rotation in nucleic acids ( NAs). The modified force field corrects overpopulations of the alpha/gamma ( g+, t) backbone that were seen in long ( more than 10 ns) simulations with previous AMBER parameter sets ( parm94-99). The force field has been derived by fitting to high-level quantum mechanical data and verified by comparison with very high-level quantum mechanical calculations and by a very extensive comparison between simulations and experimental data. The set of validation simulations includes two of the longest trajectories published to date for the DNA duplex ( 200 ns each) and the largest variety of NA structures studied to date ( 15 different NA families and 97 individual structures). The total simulation time used to validate the force field includes near 1 mu s of state-of-the-art molecular dynamics simulations in aqueous solution.