Molecular Level Investigation of Cell Penetrating Peptide Adsoption on Silica Surfaces by Classical and Enhanced Sampling Techniques.

Magnetic nanoparticles (MNPs) represent one of the most promising materials as they found application in bionanotechnology for enhanced imaging, diagnosis, and treatment of various diseases. Silica improves colloidal stability and the binding affinity for various organic molecules and as such is used to cover iron oxide NPs. One of the strategy for improving the coated MNPs might be the functionalization with organic molecules, such as cell penetrating peptides (CPPs) since they are able to enter into the cells and can enhance the physicochemical properties, adding a cell penetrating feature of the MNPs. In this work, a computational investigation on several CPPs interacting with three different silica surfaces is presented. The Molecular Dynamics techniques can be used to provide insight on the adsorption mechanism of the peptides onto the silica surface as well as and the use of enhanced technique can provide an estimation of the free energy surfaces. Here, a Well-tempered Metadynamics simulation was employed using the distance between the cell penetrating peptide and the surface as CV, to highlight the influence of surface ionization’s state on the adsorption mechanism. Although peptide binding is generally moderated by the physicochemical characteristics of the adsorbing peptide, the introduction of such a small degree of functionality onto silica particles was sufficient to produce drastic changes in the peptide’s adsorption.