View source for 5fnd


==Dynamic Undocking and the Quasi-Bound State as tools for Drug Design==
<StructureSection load='5fnd' size='340' side='right'caption='[[5fnd]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fnd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FND OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FND FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IQ5:N-(2-AZANYL-6-METHYL-1,3-BENZOTHIAZOL-5-YL)ETHANAMIDE'>IQ5</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5fnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fnd OCA], [https://pdbe.org/5fnd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fnd RCSB], [https://www.ebi.ac.uk/pdbsum/5fnd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fnd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref> 
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== Publication Abstract from PubMed ==
There is a pressing need for new technologies that improve the efficacy and efficiency of drug discovery. Structure-based methods have contributed towards this goal but they focus on predicting the binding affinity of protein-ligand complexes, which is notoriously difficult. We adopt an alternative approach that evaluates structural, rather than thermodynamic, stability. As bioactive molecules present a static binding mode, we devised dynamic undocking (DUck), a fast computational method to calculate the work necessary to reach a quasi-bound state at which the ligand has just broken the most important native contact with the receptor. This non-equilibrium property is surprisingly effective in virtual screening because true ligands form more-resilient interactions than decoys. Notably, DUck is orthogonal to docking and other 'thermodynamic' methods. We demonstrate the potential of the docking-undocking combination in a fragment screening against the molecular chaperone and oncology target Hsp90, for which we obtain novel chemotypes and a hit rate that approaches 40%.

Dynamic undocking and the quasi-bound state as tools for drug discovery.,Ruiz-Carmona S, Schmidtke P, Luque FJ, Baker L, Matassova N, Davis B, Roughley S, Murray J, Hubbard R, Barril X Nat Chem. 2017 Mar;9(3):201-206. doi: 10.1038/nchem.2660. Epub 2016 Nov 14. PMID:28221352<ref>PMID:28221352</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5fnd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baker LM]]
[[Category: Barril X]]
[[Category: Davis B]]
[[Category: Hubbard R]]
[[Category: Luque FJ]]
[[Category: Matassova N]]
[[Category: Murray J]]
[[Category: Roughley S]]
[[Category: Ruiz-Carmona S]]
[[Category: Schmidtke P]]