Single- and Double-Stranded DNA Simulations Using An Intermediate-Resolution Model

DNA microarray technology is a powerful tool for biological research, allowing scientists to track the expression patterns of thousands of genes simultaneously. To fully exploit the potential of this emerging technology, a better understanding of the physics underlying the process at the mesoscopic scale is still needed. A new intermediate resolution model for DNA molecules designed for use with discontinuous molecular dynamics (DMD) simulations is presented. The model was developed using a multiscale modeling approach in which the geometric and energetic parameters are obtained by collecting data from CHARMM-based atomistic simulations of single- and double-stranded DNA molecules with explicit solvent and counterions. The sugar, phosphate, and base in the model are each represented by single spheres connected via bonds with appropriate lengths and angles. Hydrogen bonding is modeled using an angle-dependent square-well scheme and base stacking is modeled using explicit intra-strand interactions between nearest neighbor bases. DMD simulations were performed on model single- and double-stranded DNA molecules of 12 different base sequences and several chain lengths at a variety of reduced temperatures. The model reproduces qualitatively: (1) the conformational properties of single-stranded DNA sequences as a function of temperature, (2) the temperature-dependent melting behavior of double-stranded DNA, and (3) the hybridization process in solution.