STRUCTURAL EQUILIBRIUM OF DNA REPRESENTED WITH DIFFERENT FORCE-FIELDS

We have recently indicated preliminary evidence of different equilibri um average structures with the CHARMM and AMBER force fields in explic it solvent molecular dynamics simulations on the DNA duplex d(C5T5).d( A(5)G(5)) (Feig, M. and B. M. Pettitt, 1997, Experiment vs. Force fiel ds: DNA conformation from molecular dynamics simulations. J. Phys. Che m. B. 101:7361-7363). This paper presents a detailed comparison of DNA structure and dynamics for both force fields from extended simulation times of 10 ns each. Average structures display an A-DNA base geometr y with the CHARMM force field and a base geometry that is intermediate between A- and B-DNA with the AMBER force field. The backbone assumes B form on both strands with the AMBER force field, while the CHARMM f orce field produces heterogeneous structures with the purine strand in A form and the pyrimidine strand in dynamical equilibrium between A a nd B conformations. The results compare well with experimental data fo r the cytosine/guanine part but fail to fully reproduce an overall B c onformation in the thymine/adenine tract expected from crystallographi c data, particularly with the CHARMM force field. Fluctuations between A and B conformations are observed on the nanosecond time scale in bo th simulations, particularly with the AMBER force field. Different dyn amical behavior during the first 4 ns indicates that convergence times of several nanoseconds are necessary to fully establish a dynamical e quilibrium in all structural quantities on the time scale of the simul ations presented here.