The rational design of proteins to perform particular functions is a grand challenge in modern science with the potential to revolutionize medicine, materials, and engineering. The primary obstacle is the vast size of protein sequence space making trial-and-error search intractable. This project will establish a platform encompassing a model for functional proteins that can be used to rationally design new candidates, a “gene machine” to prototype designs, and high-throughput quantitative assays to experimentally test the designed proteins. A computational-experimental feedback loop will supercharge the search through sequence space equivalent to many millions of years of natural evolution to discover novel synthetic proteins with unprecedented control over functional properties.