Computational nanoscience and multiscale modeling of DNA molecules

Molecular Dynamics is a very powerful technique for the investigation of matter at nanoscopic level. However, it’s application in many fields, such as the investigation of many relevant processes of cell biology, is restricted by issues of computational cost. Therefore, in recent years, a growing interest has been generated by the introduction of Coarse-Grained (CG) models, that allow the investigation of bigger systems for longer timescales. In this thesis, Molecular Dynamics was used in order to gain a quantitative understanding of mechanical and di.usive processes of DNA molecules in solution, and in order to parametrise a Coarse Grained model of DNA capable of a qualitative description of the mechanical behaviour of the all-atom model at equilibrium. A software package for the computation of Coarse-Grained interaction force-fields, making use of the recently developed Multiscale Coarse-Grained Method (MSCG) by Izvekov and Voth [1] was implemented. We tested and validated the method by performing a one-point-per-molecule coarse graining of TIP3P water. The resulting model was able to reproduce the fluid structure (its radial distribution function) in a satisfactory and nearly quantitative way. Finally, we applied the MSCG method to a more demanding problem, namely the parametrisation of a 3-point-per-residue coarse-grained model of double-stranded DNA. As a consequence, the agreement of the obtained CG model with the atomistic structure was still not quantitative. In particular, the helical geometry was qualitatively preserved and the Root-Mean-Square Displacement (RMSD) of the coarse-grained model was stable over the trajectory, but higher than its all-atom counterpart. We suggest several possible routes for future improvements. In particular, the explicit modeling of torsional degrees of freedom of the DNA backbone, and the use of recently introduced methods for the refinement of the MSCG estimation of force-field parameters, and a more accurate treatment of Coulombic interactions.