Abstract: The present disclosure provides systems and methods for engineering protein activity. In an aspect, described herein are new predictive models that predict protein activity from its amino acid sequence (e.g., using a trained machine learning model and a physics-based simulation model). In another aspect, new prescriptive models identify one or more candidate proteins (e.g., for use in the predictive model) that can use a multi-objective search and optimization algorithm. In another aspect, predictive and prescriptive models can be combined, e.g., with the addition of high-throughput laboratory data which has been by analyzed by a descriptive model. In another aspect, described herein are systems and methods for high-throughput automated expression of a plurality of proteins. In another aspect, described herein are systems and methods for high-throughput automated functional screening of a plurality of proteins.