Structure-based drug discovery methods are generally based on predicting the binding affinity of a ligand to a protein. Ruiz-Carmona et al. introduce a novel computational procedure termed dynamic undocking (DUck), which evaluates the structural stability of protein–ligand complexes. DUck calculates the work needed to break a key native contact and reach a quasi-bound state. In test systems, active compounds were structurally stable and presented higher quasi-bound values than inactive ones. DUck is orthogonal to existing virtual screening methods: in a fragment screening against HSP70, DUck identified novel chemotypes and had a hit rate of 38%.
References
Ruiz-Carmona, S. et al. Dynamic undocking and the quasi-bound state as tools for drug discovery. Nat. Chem. http://dx.doi.org/10.1038/nchem.2660 (2016)
Rights and permissions
About this article
Cite this article
Crunkhorn, S. Novel virtual screening approach. Nat Rev Drug Discov 16, 18 (2017). https://doi.org/10.1038/nrd.2016.272
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrd.2016.272