In this talk, several examples will be presented showing how Molecular Modeling can act as virtual microscope to have insight on molecular mechanisms. The first part will be devoted to some examples where we show how the modifications of some structural parameters can affect the efficiency of a special class of hyperbranched polymers called dendrimers as delivery systems. Recently, five parameters, called Critical Nanoscale Design Parameters (CNDP) that characterize the behavior of well-defined nanoscale building blocks such as dendrimers: size, shape, surface chemistry, flexibility/rigidity and architecture. These quantities constitute the first real attempt to propose formal parameters allowing, in principle, to control the final behavior of a given molecule. However, the CDNP are somewhat entangled, and they do not take into account explicitly the influence of the external environment as thought as the presence of polar solvent molecules, salt ions and eventually other charged molecules. In this context, we have performed many different modeling studies to explore how the efficiency of the dendrimers in binding siRNA and DNA changes upon CDNPs modification. The effect on the affinity for nucleic acids of different dendritic generations, architecture modification, flexibility of the dendritic scaffold and changing of the ligands that decorate the surface were explored in detail.

In the second part, some preliminary results will be presented about the investigation of the interaction of Cell-Penetrating Peptides (CPPs) with iron oxide nanoparticles in order to assess their potential as functionalization strategies. Magnetite protonation state strongly influences the interaction with dendrimers and CPPs. In the case of CPPs, it is interesting to notice that, the final adsorbed conformations are characterized by peptides flattened over the NP surface mainly interacting through arginine, a key residue for the peptide’s function.

In the last part, we show some preliminary results concerning a new approach that we proposed for the implementation of the Multiscale Coarse Graining method, using Wavelets as set of functions for the approximation of the force fields.