We have developed a mesoscale model of DNA in which each nucleotide is represented by three interaction sites. Our construct employs an implicit solvent scheme which allows for the treatment of denaturation/renaturation events in relevant biochemical processes. Parameterization has been accomplished to reproduce thermo-mechanical properties as a function of chain length, composition and sequence, as well as solvent ionic activity.

We have implemented our mesoscale description of DNA to study genome encapsidation in bacteriophage and nucleosome core particle assemblies. We study the insertion and ejection phases in the DNA viral encapsidation process in terms of internal capsid pressure, motor stalling events and molecular structure and stresses of confined DNA as a function of DNA flexibility. We find that models of DNA with different flexibilities give similar results for internal capsid pressure, motor stalling and strand separation, but marked differences in the the structure of the wrapped DNA. We also investigate the dependence of the stability of a nucleosome core particle assembly with sequence of the DNA wrapped around the histones. In particular, we are interested in elucidating the interplay of DNA flexibility and DNA-histone electrostatic interactions in the control of nucleosome positioning.

Both genome encapsidation and nucleosome formation are prime examples of nucleic acids undergoing extreme confinement, where it is essential to capture accurately molecular physical properties in order to fully characterize the process. Our coarse-graining scheme is applicable to the general problem of DNA control (such as the exonucleolytic manipulation of genomes) and to the design of nanoscopic devices aimed at optimizing the presentation of DNA.