Patent ID: 8718994

Claim:
A method for identifying a compound having the ability to modulate the GLP-1 receptor (GLP-1R), the method comprising the steps of: generating a first three-dimensional model of the GLP-1R; generating a second three-dimensional model of a potential modulator compound; using a computer to dock the second three-dimensional model with the first three-dimensional model; and quantifying at least one atomic interaction between the potential modulator compound and the GLP-1R, or a portion thereof, wherein the first three-dimensional model is a computer model of the GLP-1R, wherein the computer model comprises extracellular, transmembrane, and intracellular domains of GLP-1R; the second three-dimensional model is a computer model of the potential modulator compound and the potential modulator compound has a molecular weight of less than 2,000 daltons; the atomic interaction between the potential modulator compound and the GLP-1R does not interfere with the binding of native GLP-1 to the GLP-1R; the atomic interaction between the potential modulator compound and the GLP-1R comprises at least one atomic interaction between the potential modulator compound and at least one of the amino acid residues selected from the group consisting of Ser31, Thr35, Trp39, Arg43, Thr65, Phe66, Glu68, Asp67, Tyr69, Trp91, Leu89, Tyr88, Arg121, Arg102, Leu123, Glu127, Trp110 and Glu128 of the GLP-1R; and the atomic interaction between the potential modulator compound and the GLP-1R comprises at least one atomic interaction between the potential modulator compound and at least one of the amino acid residues selected from the group consisting of Arg376 and Arg380.