Multiscale modeling of nucleic acids: insights into DNA flexibility

The elastic rod theory is used together with all-atom normal mode analysis in implicit solvent to characterize the mechanical flexibility of duplex DNA. The bending, twisting, stretching rigidities extracted from all-atom simulations (on linear duplexes from 60 to 150 base pairs in length and from 94-bp minicircles) are in reasonable agreement with experimental results. We focus on salt concentration and sequence effects on the overall flexibility. Bending persistence lengths are about 20% higher than most experimental estimates, but the transition from low-salt to high-salt behavior is reproduced well, as is the dependence of the stretching modulus on salt (which is opposite to that of bending). CTG and CGG trinucleotide repeats, responsible for several degenerative disorders, are found to be more flexible than random DNA, in agreement with several recent studies, whereas poly(dA).poly(dT) is the stiffest sequence we have encountered. The results suggest that current all-atom potentials, which were parameterized on small molecules and short oligonucleotides, also provide a useful description of duplex DNA at much longer length scales.