Kinase inhibitors are often divided into multiple classes or types depending on their binding mode . Type I inhibitors are considered to bind to the "DFG-in" protein conformation while type II inhibitors bind the "DFG-out" conformation. The DFG-in conformation is sterically incompatible with the most common binding mode of type II inhibitors. Among known mutations conferring resistance to imatinib and related compounds, many exert their effect by changing the protein's conformational distribution and reducing occupancy of the favored binding state (Fig ). As a result, identifying both type I and type II inhibitors in a structure-based virtual screen of the ATP binding site is important for identification of new molecules of potential clinical utility, and requires the use of multiple protein conformations to adequately sample native-like ligand binding modes.