Community Research and Development Information Service - CORDIS

Final Report Summary - INTERACTION DESIGN (De novo design of affinity, specificity, and multispecificity in synthetic protein interaction networks)

Proteins are central to all life processes. The ability to design new or improved functions in proteins therefore holds the promise of control over the most fundamental aspects that determine health and disease. Our laboratory develops computer algorithms and experimental methods for designing new functions in proteins. During the course of the project we have developed new methods for designing immune-system antibodies to target desired molecules and methods to engineer novel molecular specificities in protein interaction networks. Recently, we extended these methods to also design novel enzymes to catalyze desired chemical transformations. To achieve these goals, we have used iterative cycles of algorithm development and experimental testing. During the course of these cycles we have seen that the stability of designed proteins improves drastically from cycle to cycle, and we have shown that some of the lessons we have learned from designing novel proteins can be extended to ill-behaved natural proteins to drastically improve their stability. Our design algorithm is general and fully automated, and can be accessed through a webserver. We have shown that the algorithm can be used to improve the stability of therapeutic antibodies, enzymes for industrial processes, and vaccine components. Our work has therefore extended the reach of design of function to areas that can make substantial contributions to research, biotechnology, and public health.

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