Maximizing the integration of virtual and experimental screening in hit discovery

Experimental and virtual screening contributes to the discovery of more than 50% of clinical candidates. Considering the similar concept and goals, early-phase drug discovery would benefit from the effective integration of these approaches.

After reviewing the recent trends in both experimental and virtual screening, the authors discuss different integration strategies from parallel, focused, sequential, and iterative screening. Strategic considerations are demonstrated in a number of real-life case studies.

Experimental and virtual screening are complementary approaches that should be integrated in lead discovery settings. Virtual screening can access extremely large synthetically feasible chemical space that can be effectively searched on GPU clusters or cloud architectures. Experimental screening provides reliable datasets by quantitative HTS applications, and DNA-encoded libraries (DEL) have enlarged the chemical space covered by these technologies. These developments, together with the use of artificial intelligence methods, represent new options for their efficient integration. The case studies discussed here demonstrate the benefits of complementary strategies, such as focused and iterative screening.