A Computational Study of the siRNA-Silica Nanoparticle Binding Process

Molecular dynamics simulations were performed to investigate the structural and energetic features related to the direct binding of a short interfering RNA (siRNA) molecule on a silica nanoparticle functionalized with 3-aminopropyltriethoxysilane (APTES) groups, immersed in a sodium chloride aqueous solution at physiological concentration. Three different grafting densities of APTES were evaluated, namely, 2.7, 1.3, and 0.65 nm–2. Structural features as a function of the grafting density were analyzed and characterized in terms of density field profiles, pair correlation functions, and hydrogen bonding. The analysis of the orientation of siRNA during the binding process suggested that the oligonucleotide anchors to the surface by one of their ends in a tilted arrangement and subsequently, it rotates toward a surface-parallel stabilized configuration. Free energy of binding between siRNA and the silica nanoparticle was computed using the adaptive biasing force scheme. The results indicate that the binding process is essentially barrierless and consistent with a thermodynamically spontaneous reaction, yielding the largest binding free energy, of about ∼−36 kcal/mol at the largest APTES grafting density. However, a favorable binding was also observed at the lowest APTES density (∼−16 kcal/mol). a fact that would be advantageous to facilitate the further release of siRNA within the cell.