High-throughput screening for modulators of protein–protein interactions: Use of photonic crystal biosensors and complementary technologies

High-throughput screening (HTS) has played an integral role in the development of small molecule modulators of biological processes. These screens are typically developed for enzymes (such as kinases or proteases) or extracellular receptors, two classes of targets with well-established colorimetric or fluorimetric activity assays. In contrast, methods for detection of protein–protein interactions lack the simplicity inherent to enzyme and receptor assays. Technologies that facilitate the discovery of small molecule modulators of protein–protein interactions are essential to the exploitation of this important class of drug targets. As described in this critical review, photonic crystal (PC) biosensors and other emerging technologies can now be utilized in high-throughput screens for the identification of compounds that disrupt or enhance protein–protein interactions (167 references).