A method of protein engineering is provided wherein a searchable computer database is created comprising entries in the form of descriptions of a location and orientation in 3D space of side chains of the constituent amino acid residues of a framework protein. A query is created which corresponds to a description of a location and orientation in 3D space of respective side chains of amino acid residues of a sample protein. The location and orientation in 3D space of constituent side-chains is preferably described as a C.alpha. C.beta. vector. The query is used to search the database and thereby identify a hit which corresponds to a framework protein having structural similarity with said sample protein. Framework protein "hits" so identified may be suitable candidates for further modification. A particular advantage of the present invention is that a modified framework protein may display one or more desired characteristics, such as a function similar to or inhibitory of the sample protein.