 |
Shoichet Lab University of California San Francisco Mission Bay Campus, QB3 Dept. of Pharmaceutical Chemistry 1700 4th Street, Box 2550 San Francisco, CA 94158-2330, USA tel: ++1 (415) 514-4253 fax: ++1 (415) 514-4260 
|
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 [8]. 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 [9]. 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 [4]. I am always happy about bug reports, but please consider reading this how-to by Simon Tatham before.
On July 6, 2008, DAIM 5.2 has been released. This version supports Sybyl atom types. To obtain it, please go to the download page.
| Peer-reviewed articles | |
| 2009 | |
| [10] | Docking screens: right for the right reasons? Peter Kolb, and John J. Irwin Curr. Top. Med. Chem. 2009, accepted. [review] |
| [9] | Structure-based discovery of β2-adrenergic receptor ligands. Peter Kolb†, Daniel M. Rosenbaum†, John J. Irwin, Juan José Fung, Brian K. Kobilka*, and Brian K. Shoichet* Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 6843-6848. [pdf] [sup] |
| [8] | Functional annotation and three-dimensional structure of Dr0930 from Deinococcus radiodurans: a close relative of Phosphotriesterase in the Amidohydrolase Superfamily. Dao Feng Xiang, Peter Kolb, Alexander A. Fedorov, Monika M. Meier, Elena V. Fedorov, Tinh T. Nguyen, Reinhard Sterner*, Steven C. Almo*, Brian K. Shoichet*, and Frank M. Raushel* Biochemistry 2009, 48, 2237-2247. [pdf] [sup] |
| 2008 | |
| [7] | A double-headed Cathepsin B inhibitor devoid of warhead. Patricia Schenker, Pietro Alfarano, Peter Kolb, Amedeo Caflisch, and Antonio Baici Prot. Sci. 2008, 17, 2145-2155. [pdf] [sup] |
| [6] | Structure-based tailoring of compound libraries for high-throughput screening:
Discovery of novel EphB4 kinase inhibitors. Peter Kolb, Catherine Berset Kipouros, Danzhi Huang, and Amedeo Caflisch Proteins: Struct. Funct. Bioinf. 2008, 73, 11-18. [pdf] [sup] |
| [5] | Discovery of kinase inhibitors by high-throughput docking and scoring based on a transferable linear
interaction energy model. Peter Kolb†, Danzhi Huang†, Fabian Dey†, and Amedeo Caflisch J. Med. Chem. 2008, 51, 1179-1188. [pdf] [sup] |
| 2006 | |
| [4] | Automatic and efficient decomposition of two-dimensional structures of
small molecules for fragment-based high-throughput docking. Peter Kolb*, and Amedeo Caflisch* J. Med. Chem. 2006, 49, 7384-7392. [pdf] |
| [3] | In silico discovery of β-secretase inhibitors. Danzhi Huang, Urs Lüthi, Peter Kolb, Marco Cecchini, Alcide Barberis, and Amedeo Caflisch J. Am. Chem. Soc. 2006, 128, 5436-5443. [pdf] [sup] |
| 2005 | |
| [2] | Discovery of cell-permeable nonpeptide inhibitors of
β-secretase. Danzhi Huang, Urs Lüthi, Peter Kolb, Karin Edler, Marco Cecchini, Stephan Audétat, Alcide Barberis, and Amedeo Caflisch J. Med. Chem. 2005, 48, 5108-5111. [pdf] [sup] |
| 2004 | |
| [1] | Automated docking of highly flexible ligands by genetic algorithms:
A critical assessment. Marco Cecchini, Peter Kolb, Nicolas Majeux, and Amedeo Caflisch J. Comput. Chem. 2004, 25, 412-422. [pdf] |
| †these authors contributed equally. *co-corresponding authors. | |
| Book chapters | |
| [1] | Fragment-based high-throughput docking. Peter Kolb, Marco Cecchini, Danzhi Huang, and Amedeo Caflisch In: Juan Alvarez and Brian K. Shoichet (Eds.) Virtual Screening. CRC Press, 2005, 349-378. [pdf] |
| Other scientific contributions |
