Target Protein Design and Preselection Analysis.

DNA-encoded library (DEL) technology utilizes affinity-based selection methods to screen chemical libraries. DEL technology possesses some unique features compared to other small molecule screening technologies, such as the use of DNA identification tags and use of target protein immobilization in the standard library screening process. Therefore, it is of great importance to ensure the target protein is properly designed for DEL selections, that the protein is of high quality, and that ligand binding sites are accessible under DEL selection conditions. Here we describe general considerations for target protein design and expression and experiments that are conducted before initiating selections to assess protein quality and validate methods that will be used for the DEL selection.