DOCKovalent is a covalent virtual screening software that was developed by Dr. London while at the Shoichet Lab at UCSF. It is based on the DOCK software with adaptations to the sampling and scoring to take into account the newly formed covalent bond, and relies on the ZINC database and ligand generation pipeline.
Kinases are extremely important for signaling and as potential drug targets, but are notoriously hard to inhibit specifically (without hitting off-targets). By targeting non conserved cysteine residues nearby kinase active sites we were able to design very specific covalent kinase inhibitors.
Through harnessing an irreversible covalent bond, a designed covalent probe could theoretically stabilize rare protein conformations. We are developing the technology to design such molecules. We are developing compounds that would bias signaling proteins to a specific activated conformation that would allow unprecedented control of signaling pathways.
The lab continually strives to advance our covalent docking technology. This includes the implementation of new algorithms for improved sampling and scoring of covalent adducts as well as systematic analysis of available covalent complexes.