Multiscale modeling of metal nanoparticles for biotechnological applications

Functionalized metal nanoparticles are supramolecular assemblies that are gaining increasing attention in biomedicine due to their broad-spectrum applicability. In this context, understanding the nano-biointerface is critical for implementing nanoparticles into medical practices, yet the structure-function relation of functionalized metal nanoparticles remains puzzling. This work discusses the design of metal nanoparticles with targeted applications from three focal points: structural modeling, method development, and biomolecular interactions. First, the NanoModeler webserver is introduced for the standardized building and parametrizing of metal nanoparticles for simulations at atomistic and coarse-grained resolutions. Second, a theoretical model is formulated to characterize the surface of charged nanoparticles, which, when combined with mesoscale simulations, clarifies the fundamental principles that enable colloidal stability at physiological conditions. Third, atomistic and coarse-grained simulations were combined to describe, at the molecular level, the non- disruptive cellular permeabilization induced by membranotropic nanoparticles to facilitate intracellular cargo delivery. The multilayered work presented here comprehends new online tools, physics-based methods, and molecular insights that expand our understanding of the structure-function relation in metal nanoparticles and contribute to the design of safe and effective nanoparticle-based therapeutic agents.