A method for generating a library of antigen binding molecules for screening for binding to an epitope of interest, said method comprising: (a) selecting a template antigen-binding molecule from a set of possible template antigen binding molecules wherein said selected template does not specifically bind the epitope of interest but is known to specifically bind another epitope, wherein said selecting comprises screening three-dimensional structures or structural models of the set of possible template antigen-binding molecules based on one or more of the following criteria: shape complementarity to the epitope of interest, physico-chemical complementarity to the epitope of interest and the predicted free energy of the interaction with the epitope of interest; (b) selecting at least one residue position in said template antigen-binding molecule for mutation, wherein said selecting comprises (i) screening the three dimensional structure and/or a three-dimensional model of the template antigen-binding molecule selected in (a) to identify residues likely to contribute to binding to the epitope of interest; or (ii) conducting multiple sequence alignment of the nucleic acid sequence of the template antigen-binding molecule selected in (a) to identify substitutable positions; and (c) selecting at least one variant residue to substitute at the at least one residue position selected in (b), wherein said selecting comprises, for each residue identified in step (b), identifying one or more amino acid substitutions that are preferred, allowed or neutral at that residue position; and (d) synthesizing one or more variants of said template antigen-binding molecule wherein said variants comprise at least one substitution identified in (c) thereby forming a library of variants of said template antigen-binding molecule. (a) selecting a template antigen-binding molecule from a set of possible template antigen binding molecules wherein said selected template does not specifically bind the epitope of interest but is known to specifically bind another epitope, wherein said selecting comprises screening three-dimensional structures or structural models of the set of possible template antigen-binding molecules based on one or more of the following criteria: shape complementarity to the epitope of interest, physico-chemical complementarity to the epitope of interest and the predicted free energy of the interaction with the epitope of interest; (b) selecting at least one residue position in said template antigen-binding molecule for mutation, wherein said selecting comprises (i) screening the three dimensional structure and/or a three-dimensional model of the template antigen-binding molecule selected in (a) to identify residues likely to contribute to binding to the epitope of interest; or (ii) conducting multiple sequence alignment of the nucleic acid sequence of the template antigen-binding molecule selected in (a) to identify substitutable positions; and (c) selecting at least one variant residue to substitute at the at least one residue position selected in (b), wherein said selecting comprises, for each residue identified in step (b), identifying one or more amino acid substitutions that are preferred, allowed or neutral at that residue position; and (d) synthesizing one or more variants of said template antigen-binding molecule wherein said variants comprise at least one substitution identified in (c) thereby forming a library of variants of said template antigen-binding molecule.