Abstract
AbstractBiological engineering aims to enhance biological systems by designing proteins with improved catalytic properties or ligands with enhanced function. Typically, applications permit designing proteins, e.g., an enzyme in a biodegradation reaction, or ligands e.g., a drug for a target receptor, but not both. Yet, some applications can benefit from a more flexible approach where both the protein and ligand can be designed or modified together to enhance a desired property. To meet the need for this co-design capability, we introduce a novel co-design paradigm and demon- strate its application to Ndh2-quinone pairings to enhance their binding affinity. Ndh2, type-II NADH dehydrogenase, is an enzyme found in certain bacteria that facilities extracellular electron transfer (EET) when interacting with exogenous quinone mediators. This interaction leads to the generation of a detectable electric current that can be used for biosensing applications. Our results demonstrate the benefits of the co-design paradigm in realizing Ndh2-quinone pairings with enhanced binding affinities, therefore highlighting the importance of considering protein-ligand engineering from a holistic co-design perspective.
Publisher
Cold Spring Harbor Laboratory