Modified polypeptides stabilized in a desired conformation and methods for producing same

A method for identifying a compound capable of modulating the interaction of an integrin and a ligand comprising the steps of:

• (a) providing a modified integrin I-domain polypeptide comprising (i) the amino acid sequence of SEQ ID NO:6 containing at least one disulfide bond, said polypeptide containing amino acid substitutions selected from the group consisting of Q163C/Q309C and D294C/Q311C;
• or (ii) the amino acid sequence of SEQ ID NO:5 containing at least one disulfide bond, said polypeptide containing amino acid substitutions selected from the group consisting of K287C/K294C, E284C/E301C, L161C/F299C, K160C/F299C, L161C/T300C, and L289C/K294C, such that said modified I-domain polypeptide is stabilized in a desired conformation,
• (b) contacting the modified integrin I-domain polypeptide with a ligand of the integrin in the presence and absence of a test compound;
• and
• (c) detecting binding between the modified integrin I-domain polypeptide and said ligand,
• to thereby identify a compound capable of modulating the interaction between an integrin and a ligand.