Inverse design of proteins with hydrophobic and polar amino acids

A two amino acid (hydrophobic and polar) scheme is used to perform the design on target conformations corresponding to the native states of twenty single chain proteins. Strikingly, the percentage of successful identification of the nature of the residues benchmarked against naturally occurring proteins and their homologues is around 75 % independent of the complexity of the design procedure. Typically, the lowest success rate occurs for residues such as alanine that have a high secondary structure functionality. Using a simple lattice model, we argue that one possible shortcoming of the model studied may involve the coarse-graining of the twenty kinds of amino acids into just two effective types.