Improved DNA Intermediate-Resolution Model for Biological Applications

A recently developed intermediate resolution model for DNA designed for use with discontinuous molecular dynamics (DMD) simulations has been improved by implementing a more accurate description of base stacking interactions. The model was developed using a multiscale modeling approach in which the geometric and energetic parameters are obtained by collecting data from 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. The model was applied to study the temperature-dependent melting behavior of double-stranded DNA, the hybridization process from initially single-stranded molecules into a dynamic double helical structure, and the flexibility of self-assembled DNA nanostructures.