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De novo design of affinity, specificity, and multispecificity in synthetic protein interaction networks

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A system for the design of novel proteins

European researchers have developed an algorithm-based platform for generating synthetic proteins of unique specificity and affinity. This tool has the capacity to be used in various biomedical applications.

Fundamental Research

Proteins are central to all life processes and thus play an instrumental role in health and disease. The ability to design novel functions in proteins is therefore of fundamental importance for providing insight into uncharted pathways and for generating novel therapeutics. To achieve this, the EU-funded INTERACTION DESIGN (De novo design of affinity, specificity, and multispecificity in synthetic protein interaction networks) project combined genetics and molecular biology to generate novel protein networks with predetermined levels of specificity and affinity. Initially, researchers utilised a synthetic network that employed an acyl carrier protein and different binders. By varying the affinity of the protein to its binders through residue substitutions, scientists studied affinity and specificity. These attributes were further increased by experimental in vitro selection of the variants with high affinity. Subsequently, the consortium focused on antibody and enzyme generation, and employed computer algorithms and experimental methods to target desired molecules. This approach endowed novel molecular specificities in protein interaction networks. Overall, scientists observed that iterative cycles of algorithm development and experimental testing drastically improved the stability of designed proteins. Apart from therapeutic antibodies, enzyme and vaccine components, their fully automated design algorithm could also be employed to alter the stability of proteins implicated in various diseases. Taken together, the INTERACTION DESIGN system has the potential to contribute to research, biotechnology and public health.


Synthetic proteins, INTERACTION DESIGN, acyl carrier protein, antibody, enzyme

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