Structure-based identification of candidate compounds using three dimensional structures and models of Fc receptors

A method of structure-based identification of candidate compounds for binding to Fc receptor (FcR) proteins, comprising:

• (a) constructing a three dimensional structure of an FcR protein defined by atomic coordinates selected from the group consisting of:
• (i) atomic coordinates represented in a table selected from the group consisting of Table 1, Table 2, Table 3, Table 4 and Table 5;
• and,
• (ii) atomic coordinates that define a three dimensional structure, wherein at least 50% of at least one domain of said structure has an average root-mean-square deviation (RMSD) from backbone atoms in secondary structure elements in at least one domain of a three dimensional structure represented by said atomic coordinates of (i) of less than about 1.5 Å;
• (b) performing computer-assisted, structure based drug design with said structure of (a);
• and
• (c) identifying at least one candidate compound structure that is predicted to have a compatible conformation with a target site on the constructed structure of the FcR protein such that the compound having the compound structure is predicted to bind to the FcR protein.

A method of structure-based identification of candidate compounds for binding to Fc receptor (FcR) proteins, comprising:

• (a) constructing a three dimensional structure of an FcR protein selected from the group consisting of FcγR and FcεR. using as a template a three dimensional structure of a FcγRIIa protein (SEQ ID NO:3), wherein said three dimensional structure of a FcγRIIa protein is constructed from atomic coordinates determined by X-ray diffraction of an orthorhombic crystal of FcγRIIa protein (SEQ ID NO:3) molecules arranged in a space group P21212, so as to form a unit cell of dimensions a=78.80 Å, b=100.55 Å, c=27.85 Å;
• (b) performing computer-assisted, structure based drug design with said structure of (a);
• and
• (c) identifying at least one candidate compound structure that is predicted to have a compatible conformation with a target site on the constructed structure of the FcR protein such that the compound having the compound structure is predicted to bind to the FcR protein.