Identifying substrates of amidohydrolases. The preferred substrate class of Dr0930 (PDB 3FDK) from Deinococcus radiodurans was successfully identified with the high-energy intermediate (HEI) approach to docking . Although docking was clearly able to enrich lactones (the true substrate),it also enriched lactams, which are not turned over. Dr0930 represents an enzyme where substrate recognition goes beyond physical complementarity of the enzyme for an HEI and where the cost of forming the HEI from the ground state also plays an important role; this energy difference between ground and excited states presumably distinguishes many of the lactams from the lactones and many of the stabilized lactones from those aliphatic δ-lactones that are among the best substrates.
Finding inhibitors of GPCRs with DOCK. Using the recently solved x-ray structure of the β2-adrenergic receptor (PDB 2RH1), we succeeded in identifying six novel ligands . Interestingly, two of these ligands represent novel chemotypes and demonstrate the potential of docking for discovering unprecedented scaffolds. All the compounds discovered are inverse agonists and, intriguingly, compound 1 is the most efficacious inverse agonist described so far.
I am still developing and maintaining DAIM (Decomposition And Identification of Molecules), a program for fragment generation in the context of fragment-based docking and analysis of molecule libraries. For more information and potential other uses of DAIM see the manual or reference . I am always happy about bug reports, but please consider reading this how-to by Simon Tatham before.
On September 7, 2009 DAIM 5.3 has been released. The update contains several improvements and allows more user choices with respect to the bonds that DAIM cuts. Essentially, it is now possible to override all of the default unbreakable bond definitions. To obtain it, please go to the download page.