DEL screening that moves beyond simple hit discovery
DNA-Encoded Libraries (DELs) enable the deep interrogation of chemical space and offer a powerful route to hit identification, particularly for challenging targets. However, the value of a DEL campaign is not defined by the number of compounds screened, but by the confidence in the hits that emerge and their ability to progress within your project.
Why DEL screening often falls short
DEL technology is widely applied, but selection output alone does not guarantee meaningful results. Enriched compounds may reflect poor selection conditions rather than true target engagement. In complex systems, low protein quality, incomplete target occupancy or target disruption during pulldown can obscure compound binding, making it difficult to distinguish real hits from artifacts.
As a result, DEL campaigns may generate extensive datasets without providing sufficient confidence in which compounds to advance.
What ZoBio’s DEL screening services deliver
The objective of DEL screening is not just hit identification, but the generation of validated hit matter with defined binding behavior and clear potential for progression. At ZoBio, DEL screening is embedded within a broader, structure-guided discovery framework. By combining high-quality protein science, quantitative binding assays, and structural biology, DEL outputs are not only identified but also understood, validated, and positioned for follow-up.
This approach ensures that selection results can be interpreted in context and translated into meaningful next steps for your program.
Experience with challenging targets
DEL screening is particularly suited to targets that are difficult to address using conventional approaches, including proteins with shallow or poorly defined binding sites and protein–protein interactions. The large size and diversity of DELs allow deep sampling of chemical space, increasing the likelihood of identifying ligands with sufficient interaction networks to achieve meaningful affinity for your target.
At ZoBio, DEL campaigns are applied selectively and strategically, guided by target biology, structural insight, and project objectives.
How we structure DEL screening campaigns
DEL screening is most effective when it is not treated as an isolated activity.
- Campaigns begin with carefully characterized, crystallography-grade protein to ensure functional integrity across assays and enable seamless transition into structural studies.
- Quantitative binding data, typically generated using SPR and complementary biophysical methods, is used to define selection conditions and understand target engagement.
- Following selection, sequencing outputs are analyzed using in-house tools that enable interactive interrogation of enrichment patterns and support joint decision making with your team.
- Hits are resynthesized off-DNA (externally) and validated using orthogonal biochemical and/or biophysical assays to confirm binding and eliminate artifacts.
- Validated hits are advanced to structural studies, including X-ray crystallography, to determine binding modes and guide further optimization.
How ZoBio’s DEL Screening approach differs
Many DEL workflows simply focus on the selection step, but the resulting hits may not be interpretable with confidence and progressed. At ZoBio, we integrate DEL screening with protein science, quantitative binding data, and structural biology. This enables the design of selection strategies that reliably probe specific mechanisms of action, including competitive or allosteric binding.
By combining controlled selection conditions with quantitative insight, DEL outputs can be interpreted with greater confidence, particularly in complex systems, allowing you to make informed progression decisions.
From DEL output to validated hit matter
DEL screening is most valuable when the path from selection to validation is clearly defined. Rather than delivering lists of enriched compounds, campaigns are structured to generate validated hit matter that you can progress into follow-up studies.
This includes off-DNA synthesis, orthogonal validation, and structural characterization, enabling a clearer understanding of how compounds interact with your target.