Proteins are chains of simple molecules called amino acids. The three-dimensional shape of a protein and its amino acid composition define its biological function. Over millions of years, living organisms have evolved and produced a large catalog of proteins. By exploring the space of possible amino-acid sequences, protein engineering aims at similarly designing tailored proteins with specific desirable properties. In Computational Protein Design (CPD), the challenge of identifying a protein that performs a given task is defined as the combinatorial optimization problem of a complex energy function over amino acid sequences. In this paper, we introduce the CPD problem and some of the main approaches that have been used to solve it. We then show how this problem directly reduces to Cost Function Network (CFN) and 0/1LP optimization problems. We construct di erent real CPD instances to evaluate CFN and 0/1LP algorithms as implemented in the toulbar2 and cplex solvers. We observe that CFN algorithms bring important speedups compared to the CPD platform osprey but also to cplex.