Natural enzymes and receptors exhibit remarkable properties in catalysis and molecular recognition through the pre-organization of functional groups within three-dimensional cavities. However, the functional groups in proteins are limited. While synthetic catalysts incorporate a greater diversity of elements and functional groups, they generally lack the exquisite substrate recognition and fast kinetics afforded by proteins under mild conditions. We aim to combine the benefits of biomolecular scaffolds and synthetic catalysts within hybrid systems. We use soluble biomolecular nanostructures and solid bio-nanomaterials as scaffolds and synthetically modify the cavities inherent to these structures to create enzyme-mimicking active sites, which we anticipate will exhibit new catalytic mechanisms. The catalysts and receptors created through this research have broad potential applications, including synthetic methodology, environmental remediation, therapeutics, sensing, and energy.

Project Areas


DNA nanotechnology is extraordinarily powerful in creating complex 2D and 3D structures featuring designer cavities. By tailoring these cavities using synthetic chemistry, we are creating hybrid catalysts that achieve rate enhancement through pre-organization of multiple abiotic components. Taking advantage of the information-encoding properties of DNA, we are developing combinatorial approaches for rapidly evaluating the activity of billions of DNA nanocatalysts. The programmability of DNA creates opportunities to make these catalysts stimuli-responsive. In the longer term, these DNA nanoscaffolds could be plugged into complex 2D and 3D DNA arrays, allowing multiple catalysts to be displayed in precise configurations.




Embedding abiotic metal complexes within protein scaffolds to create artificial metalloenzymes is a promising strategy to engender new reactivity and enhance selectivity. However, to harness the full power of protein-based active sites, new directed evolution methodologies are needed that allow coupling of an abiotic cofactor to millions of protein mutants, followed by identification of the most active variants. We are developing such methodologies and using them together with rational protein engineering and mechanistic analysis to discover catalysts with enhanced reactivity.


Protein-based materials are promising scaffolds for creating enzyme-mimicking catalysts because they contain large nanopores that are lined with diverse functional groups. We are embedding abiotic metal complexes site-specifically within porous protein frameworks to create enzyme-mimicking active sites. This approach combines the tunable, well-defined active sites of homogeneous catalysts with the recyclability of heterogeneous catalysts. We ultimately aim to create multi-functional materials by employing protein building blocks that exhibit independent catalytic or stimuli-responsive properties.




Receptors are essential tools in biomedicine and chemical biology, with applications in diagnostics, targeted therapeutics, medical imaging, and drug delivery. Despite tremendous advances, there is an ongoing need for new receptors. It remains extremely challenging to mimic the exquisite guest-binding sites of natural receptors, which consist of pre-organized functional groups that are chemically diverse and optimized through evolution. We are developing combinatorial approaches to rapidly discover new receptors bearing chemically diverse functional groups within three-dimensional cavities.

Potential Applications


We are harnessing second-sphere interactions and pre-organization effects to accelerate synthetic transformations under mild reaction conditions and to achieve regio- and stereo-selective modification of complex substrates.


We are developing responsive catalysts that can be used for biomarker detection, modification of therapeutically relevant targets, or modulation of cell-based therapies. We are also developing artificial receptors with potential applications in therapeutics and diagnostics.


We are deploying evolved enzymes and enzyme-mimicking catalysts for degradation and recycling of recalcitrant waste materials. Additionally, we are exploring the catalytic breakdown of pollutants and toxins using biodegradable scaffolds.


We are developing metalloenzyme-mimicking catalysts for transformations relevant in the efficient storage and utilization of renewable energy.