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The controlled formation of nanoparticles with optimum characteristics and functional aspects has proven successful via peptide-mediated nanoparticle synthesis. However, the effects of the peptide sequence and binding motif on surface features and physicochemical properties of nanoparticles are not well-understood. In this study, we investigate in a comparative manner how a specific peptide known as Pd4 and its two known variants may form nanoparticles both in an isolated state and when attached to a green fluorescent protein (GFPuv). More importantly, we introduce a novel computational approach to predict the trend of the size and activity of the peptide-directed nanoparticles by estimating the binding affinity of the peptide to a single ion. We used molecular dynamics (MD) simulations to explore the differential behavior of the isolated and GFP-fused peptides and their mutants. Our computed palladium (Pd) binding free energies match the typical nanoparticle sizes reported from transmission electron microscope pictures. Stille coupling and Suzuki–Miyaura reaction turnover frequencies (TOFs) also correspond with computationally predicted Pd binding affinities. The results show that while using Pd4 and its two known variants (A6 and A11) in isolation produces nanoparticles of varying sizes, fusing these peptides to the GFPuv protein produces nanoparticles of similar sizes and activity. In other words, GFPuv reduces the sensitivity of the nanoparticles to the peptide sequence. This study provides a computational framework for designing free and protein-attached peptides that helps in the synthesis of nanoparticles with well-regulated properties.
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Molecular recognition of enzymes and modulation of enzymatic activity by nanoparticle conformational sensors
Regulation of enzyme activity is key to dynamic processes in biology but is difficult to achieve with synthetic systems. We here report molecularly imprinted nanoparticles with strong binding for the N- and C-terminal peptides on lysozyme. Binding affinity for the enzyme correlated with conformational flexibility of the peptides in the protein structure. Significantly, binding at the C-terminus of lysozyme enhanced the performance of the enzyme at elevated temperatures and that at the N-terminus lowered the enzyme activity. These nanoparticles, when clicked onto magnetic nanoparticles, could also be used to fish out the protein of interest from a mixture in a single step.
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- Award ID(s):
- 2002659
- PAR ID:
- 10319572
- Date Published:
- Journal Name:
- Chemical Communications
- Volume:
- 58
- Issue:
- 11
- ISSN:
- 1359-7345
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D1CC05699A
