CompNanozymes · Metal-dependent catalysis of nanozymes: First steps towards computational nanoenzymology
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-06-01 → 2021-05-31
- EU contribution
- €183,473
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Metal-dependent catalysis of nanozymes: First steps towards computational nanoenzymology
Summary: Monolayer-protected gold nanoparticles (MPGNs) can be functionalized to produce nanodevices with unique properties. These have led to a wide range of applications in fields including pollutant removal, chemosensing, cancer diagnostics and therapy, and even catalysis. The molecules forming the outer coating monolayer are the main contributor to the nanoparticle’s functionality, however, its fundamental behavior at the level of the outer coating monolayer remains poorly understood, limiting our ability to rationally design functionalized MPGNs. We focused on MPGN-based artificial enzymes - so called nanozymes - that are a novel, highly promising, and yet poorly understood nanoparticle-based technology with potentially revolutionary applications for human health (e.g. gene therapy) and technology. Particularly, we studied a new class of nanozymes with promising ribonuclease-like activity., in which the nanocatalysis is facilitated by metal ion(s) chelated by the coating molecules of MPGNs. We used simulations flanked by experimental methods including nuclear magnetic resonance (NMR) and kinetic measurements, to dissect how MPGN-based nanozymes operate at the atomic level. Objectives: Objective 1. To understand the structure and dynamics of the nanozyme/substrate interface. We studied 2 structurally similar gold nanoparticles that cleave an RNA model system with different efficiency. Using our closed-loop approach, we revealed differently preorganized coating monolayers of these nanosystems allowing a different nature of substrate recognition. We showed that more efficient nanozyme mimics two-metal-ion enzymes for nucleic acid processing. Objective 2. To understand nanozyme reactivity in order to increase the catalytic efficiency of monolayer protected gold nanoparticles. Here, we focused on a new generation of DNA cleaving nanozymes. Having solved the ex-novo parametrization and MD setup, we run a series of classical MD simulations to detect and characterize the formation of Michaelis-Menten complexes at the nanozyme/substrate interface. Our simulations returned two possible prereactive states and we thus clarified the single metal ion mechanism of this new class of nanonucleases.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA · GenovaCoordinatorItaly
Links
Data: CORDIS, © European Union