V-SYNTHES: A New Digital Tool for Drug Development

April 14, 2022 | | 6 min read
Problems in Novel Drug Development

Most drugs work by binding to protein targets, called receptors, in or around a cell. Investigating new drugs has typically been done by screening a physical library of existing compounds for a potential match to a known receptor, testing them one by one in real cell cultures, and further modifying the promising prospects to maximize a factor called binding affinity. A high binding affinity is important because it makes a drug more likely to act upon a receptor and ultimately produce the desired effects. The difficulty of drug design is maximizing this parameter, which effectively results in a more efficient drug. 

A New Solution

A new technology, developed by researchers at the USC Dornsife College of Letters, Arts and Sciences and the UNC School of Medicine, appears to address these issues. V-SYNTHES – virtual synthon hierarchical enumeration screening – is a computational method that requires a fraction of the computational resources while still screening libraries of compounds thousands of times faster than before and with a success rate over twice as high.


Figure 1. Red: Scaffold; Green, Blue, Purple: Synthons. These chemical building blocks combine to fit the shape of a target receptor.

Figure 2. Summary of the V-SYNTHES process. Credit: Vsevolod Katritch, Ph.D. https://katritch.usc.edu/

Implementation of V-SYNTHES in Drug Development
  1. Mohs, R. C.; Greig, N. H. Drug Discovery and Development: Role of Basic Biological Research. Alzheimer’s & Dementia: Translational Research & Clinical Interventions 2017, 3 (4), 651–657., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725284.
  2. Austin, D.; Hayford, T. Research and development in the pharmaceutical industry. https://www.cbo.gov/publication/57126 (accessed Feb 23, 2022).
  3. Deane, C.; Mokaya, M. A Virtual Drug-Screening Approach to Conquer Huge Chemical Libraries. Nature 2021, 601 (7893), 322–323., https://www.nature.com/articles/d41586-021-03682-1.
  4. Real space. https://enamine.net/compound-collections/real-compounds/real-space-navigator (accessed Feb 23, 2022).
  5. Joy, D. S. Now scientists can efficiently screen billions of chemical compounds to find effective new drug therapies > news > USC dornsife. https://dornsife.usc.edu/news/stories/3599/now-scientists-can-efficiently-screen-billions-of-chemical-compo/ (accessed Feb 23, 2022).
  6. Derewicz, M. Scientists unveil drug discovery tool to screen more than 11 billion compounds. https://news.unchealthcare.org/2021/12/scientists-unveil-drug-discovery-tool-to-screen-more-than-11-billion-compounds (accessed Feb 23, 2022).