Abstract: A method is provided of selecting a compound that (a) binds a receptor, and (b) on binding the receptor, induces a perturbation in the conformation of the receptor, which conformational perturbation is correlated with a particular pharmacological activity.

Abstract: The present invention provides methods whereby the positions of peptide amide groups that are labeled with a heavy hydrogen in a polypeptide or protein can be localized at high resolution. The methods are useful for determining which peptide amide groups in a polypeptide or protein are accessible to solvent, mapping the binding site and/or binding surface of a binding protein, and/or studying allosteric or other conformational changes in a polypeptide or protein which alter the rates at which certain peptide amide hydrogens exchange with solvent.

Abstract: The present invention provides methods of identifying hot-spot residues for one or both members of a receptor-ligand complex of interest. Further provided are methods of using receptor hot-spot residues to identify compounds that functionally bind a receptor in a manner that mimics the binding of a known ligand for the receptor.