Exemplary embodiments relate to a protein engineering pipeline configured to optimize or improve proteins for specified functions. The problem space of such a task can grow quickly based on the sequence of the protein being optimized and the functions for which the protein is being designed. The solutions described herein allow the problem space to be efficiently searched by applying a combination of a protein design pipeline and an evaluation procedure performed on a quantum computer. As a result, single or multiple amino acid substitutions at a site of interest may be predicted in order to generate optimized protein variants.