Abstract
Background: The yeast two-hybrid system is the most widely used genetic assay to identify and characterize novel protein interactions. Over the past decade, the system has been adapted to cover an increasingly wide range of applications, including various tasks within the drug discovery and development process. Objective: We highlight the role of different two-hybrid systems within the drug discovery process, including target identification and validation and the selection of affinity reagents for protein targets, such as peptides and small molecules. Methods: We have focused on applications where the two-hybrid system has been used to great advantage and have sought to put a special emphasis on less conventional but promising approaches, such as the identification of agents which block therapeutically relevant protein interactions. Conclusions: The yeast two-hybrid system has evolved from a method mainly used in basic research to a collection of versatile screening systems with the potential to affect many different aspects of drug discovery today.
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