CompNanozymes · Metal-dependent catalysis of nanozymes: First steps towards computational nanoenzymology

The functionalization of monolayer-protected gold nanoparticles is at the frontier of nanotechnology, with innovative applications emerging in fields such as nanomedicine, chemosensing, and catalysis. Here, we focus on nanomaterial-based artificial enzymes called nanozymes, which have been shown to be highly stable and low-cost alternatives to natural enzymes in a wide range of applications. For example, the self-organization of Zn complexes on the surface of gold nanozymes has been shown to generate multiple bimetallic catalytic sites capable of promoting the cleavage of an RNA model substrate. This two-metal-aided mechanism found in nanozymes closely resembles that used by many metalloenzymes that process nucleic acids in cells. However, the complex, hybrid, and flexible nature of the outer coating monolayer of nanozymes has so far made it difficult to investigate the structure and dynamics of these multifunctional chemical systems, which have reached a level of complexity resembling that of proteins. Within this context, this project’s ambition is to use classical and hybrid QM/MM simulations coupled to free-energy computation, integrated with experiments, to study the metallo-dependent functionality and mechanisms of nanozymes that cleave nucleic acid model substrates. Through CompNanozymes, the fellow will thus acquire additional expertise in computational simulations, completing his research skill set and allowing him to grow into an independent group leader. Success will also fill the large knowledge gap in our understanding of nanoparticle structure-function relationships in nanozymes, advancing the field of computational nanodesign and directly impacting nanochemistry as a whole.