Prediction of amino acid sequence from structure

We have developed a method for the prediction of an amino acid sequence tha t is compatible with a three-dimensional backbone structure. Using only a b ackbone structure of a protein as input, the algorithm is capable of design ing sequences that closet!: resemble natural members of the protein family to which the template structure belongs. Ln general. the predicted sequence s are shown to have multiple sequence profile scores that are dramatically higher than those of random sequences, and sometimes better than some of th e natural sequences that make up the superfamily. As anticipated. highly co nserved but poorly predicted residues are often those that contribute to th e functional rather than structural properties of the protein. Overall, our analysis suggests that statistical profile scores of designed sequences ar e a novel and valuable figure of merit for assessing and improving protein design algorithms.