A method for identifying a site-specific conformational change in the structure of a target protein upon specific binding of an agent to an allosteric site of the protein, the method comprising: a. contacting the target protein with the agent in a first sample, wherein the target protein is labeled at a first amino acid residue with a second harmonic-active moiety having a net orientation at an interface, wherein the first amino acid residue is proximal to an active site on the target protein, wherein the target protein has been pre-incubated with a natural or synthetic ligand that is known to bind to the active site, and wherein a first detectable signal is generated by the second harmonic-active moiety using a surface selective technique; b. contacting the target protein with the agent in a second sample, wherein the target protein is labeled at a second amino acid residue with a second harmonic-active moiety having a net orientation at an interface, wherein the second amino acid residue is located in a region of the target protein that differs from the location of the first amino acid residue and is more distant from the active site than the first amino acid residue, and wherein a second detectable signal is generated by the second harmonic-active moiety using a surface selective technique; and c. comparing the first detectable signal with the second detectable signal, wherein a detectable signal indicates a conformational change in the structure of the target protein at the site of a labeled amino acid residue when the agent binds to the target protein; and wherein the agent binds specifically to an allosteric site on the target protein if the agent induces a conformational change in the structure of the target protein at the site of one labeled amino acid residue but does not induce a conformational change in the structure of the target protein at the site of the other labeled amino acids residue. a. contacting the target protein with the agent in a first sample, wherein the target protein is labeled at a first amino acid residue with a second harmonic-active moiety having a net orientation at an interface, wherein the first amino acid residue is proximal to an active site on the target protein, wherein the target protein has been pre-incubated with a natural or synthetic ligand that is known to bind to the active site, and wherein a first detectable signal is generated by the second harmonic-active moiety using a surface selective technique; b. contacting the target protein with the agent in a second sample, wherein the target protein is labeled at a second amino acid residue with a second harmonic-active moiety having a net orientation at an interface, wherein the second amino acid residue is located in a region of the target protein that differs from the location of the first amino acid residue and is more distant from the active site than the first amino acid residue, and wherein a second detectable signal is generated by the second harmonic-active moiety using a surface selective technique; and c. comparing the first detectable signal with the second detectable signal, wherein a detectable signal indicates a conformational change in the structure of the target protein at the site of a labeled amino acid residue when the agent binds to the target protein; and wherein the agent binds specifically to an allosteric site on the target protein if the agent induces a conformational change in the structure of the target protein at the site of one labeled amino acid residue but does not induce a conformational change in the structure of the target protein at the site of the other labeled amino acids residue.