Sequence-dependent elastic properties of DNA

Harmonic elastic constants of 3-11 bp duplex DNA fragments were evaluated u sing four 5 ns unrestrained molecular dynamics simulation trajectories of 1 7 bp duplexes with explicit inclusion of solvent and counterions. All simul ations were carried out with the Cornell cf nl. force-field and particle me sh Ewald method for long-range electrostatic interactions. The elastic cons tants including anisotropic bending and all coupling terms were derived by analyzing the correlations of fluctuations of structural properties along t he trajectories. The following sequences have been considered: homopolymer d(ApA)(n) and d(GpG)(n), and alternating d(GPC)(n), and d(APT)(n),. The cal culated values of Elastic constants are in very good overall agreement with experimental values for random sequences. The atomic-resolution molecular dynamics approach, however, reveals a pronounced sequence-dependence of the stretching and torsional rigidity of DNA, while sequence-dependence of the bending rigidity is smaller for the sequences considered. The earlier pred icted twist-bend coupling emerged as the most important cross-term for frag ments shorter than one helical turn. The calculated hydrodynamic relaxation times suggest that damping of bending motions mag: play a role in molecula r dynamics simulations of long DNA fragments. A comparison of elasticity ca lculations using global and local helicoidal analyses is reported, The calc ulations reveal the importance of the fragment length definition. The prese nt work shows that large-scale molecular dynamics simulations represent a u nique source of data to study various aspects of DNA elasticity including i ts sequence-dependence. (C) 2000 Academic Press.