Compositions and methods involving nuclear hormone receptor site II

A method of designing a ligand of Site II comprising:

• (a) modeling all or any part of a Site II, wherein said Site II is a structure defined by structure coordinates that describe conserved residue backbone atoms having a root mean square deviation of not more than 2.0 Å from the conserved residue backbone atoms described by the structure coordinates of amino acids E537-V543, L566, G567, Q570-W577, S599-A607, W610, R611, R614, Q615, P625, Y663, L664 and K667 of SEQ ID NO:13 according to Table I;
• and
• (b) based on said modeling, designing a chemical entity that has structural and chemical feature complementarity with all or any part of said Site II.

A ligand of a Site II, wherein said Site II is a structure defined by structure coordinates that describe conserved residue backbone atoms having a root mean square deviation of not more than 2.0 Å from the conserved residue backbone atoms described by the structure coordinates of amino acids E537-V543, L566, G567, Q570-W577, S599-A607, W610, R611, R614, Q615, P625, Y663, L664 and K667 of SEQ ID NO:13 according to Table I.

A mutant NHR, or a mutant portion of an NHR, comprising one or more amino acid mutations in Site II.

A method of measuring the binding of a test molecule to Site II comprising:

• (a) incubating an NHR with a ligand of Site II and said test molecule;
• and
• (b) measuring the ability of said test molecule to compete for binding to said Site II with said ligand, wherein said ability to compete is the measure of binding of said test molecule to Site II.