1wcc: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
Fragment screening offers an alternative to traditional screening for | Fragment screening offers an alternative to traditional screening for discovering new leads in drug discovery programs. This paper describes a fragment screening methodology based on high throughput X-ray crystallography. The method is illustrated against five proteins (p38 MAP kinase, CDK2, thrombin, ribonuclease A, and PTP1B). The fragments identified have weak potency (>100 microM) but are efficient binders relative to their size and may therefore represent suitable starting points for evolution to good quality lead compounds. The examples illustrate that a range of molecular interactions (i.e., lipophilic, charge-charge, neutral hydrogen bonds) can drive fragment binding and also that fragments can induce protein movement. We believe that the method has great potential for the discovery of novel lead compounds against a range of targets, and the companion paper illustrates how lead compounds have been identified for p38 MAP kinase starting from fragments such as those described in this paper. | ||
==About this Structure== | ==About this Structure== | ||
| Line 13: | Line 13: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferred entry: 2 | [[Category: Transferred entry: 2 7.11 1]] | ||
[[Category: Cleasby, A.]] | [[Category: Cleasby, A.]] | ||
[[Category: Frederickson, M.]] | [[Category: Frederickson, M.]] | ||
| Line 19: | Line 19: | ||
[[Category: Jhoti, H.]] | [[Category: Jhoti, H.]] | ||
[[Category: Murray, C.]] | [[Category: Murray, C.]] | ||
[[Category: Reilly, M | [[Category: Reilly, M O.]] | ||
[[Category: Tickle, I.]] | [[Category: Tickle, I.]] | ||
[[Category: CIG]] | [[Category: CIG]] | ||
| Line 28: | Line 28: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:42:49 2008'' | ||
Revision as of 16:42, 21 February 2008
|
SCREENING FOR FRAGMENT BINDING BY X-RAY CRYSTALLOGRAPHY
OverviewOverview
Fragment screening offers an alternative to traditional screening for discovering new leads in drug discovery programs. This paper describes a fragment screening methodology based on high throughput X-ray crystallography. The method is illustrated against five proteins (p38 MAP kinase, CDK2, thrombin, ribonuclease A, and PTP1B). The fragments identified have weak potency (>100 microM) but are efficient binders relative to their size and may therefore represent suitable starting points for evolution to good quality lead compounds. The examples illustrate that a range of molecular interactions (i.e., lipophilic, charge-charge, neutral hydrogen bonds) can drive fragment binding and also that fragments can induce protein movement. We believe that the method has great potential for the discovery of novel lead compounds against a range of targets, and the companion paper illustrates how lead compounds have been identified for p38 MAP kinase starting from fragments such as those described in this paper.
About this StructureAbout this Structure
1WCC is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Fragment-based lead discovery using X-ray crystallography., Hartshorn MJ, Murray CW, Cleasby A, Frederickson M, Tickle IJ, Jhoti H, J Med Chem. 2005 Jan 27;48(2):403-13. PMID:15658854
Page seeded by OCA on Thu Feb 21 15:42:49 2008