5lo5
From Proteopedia
(Difference between revisions)
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==HSP90 WITH indole derivative== | ==HSP90 WITH indole derivative== | ||
| - | <StructureSection load='5lo5' size='340' side='right' caption='[[5lo5]], [[Resolution|resolution]] 1.44Å' scene=''> | + | <StructureSection load='5lo5' size='340' side='right'caption='[[5lo5]], [[Resolution|resolution]] 1.44Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5lo5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LO5 OCA]. For a <b>guided tour on the structure components</b> use [http:// | + | <table><tr><td colspan='2'>[[5lo5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LO5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LO5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=70M:3-[4-[4-(4-cyanophenyl)piperazin-1-yl]butyl]-6-oxidanyl-1~{H}-indole-5-carbonitrile'>70M</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=70M:3-[4-[4-(4-cyanophenyl)piperazin-1-yl]butyl]-6-oxidanyl-1~{H}-indole-5-carbonitrile'>70M</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5lo5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lo5 OCA], [http://pdbe.org/5lo5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lo5 RCSB], [http://www.ebi.ac.uk/pdbsum/5lo5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lo5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://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> | [[http://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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Drug-target residence time (tau), one of the main determinants of drug efficacy, remains highly challeng-ing to predict computationally and, therefore, is usually not considered in the early stages of drug de-sign. Here, we present an efficient computational method, tau-random acceleration molecular dynamics (tauRAMD), for the ranking of drug candidates by their residence time and obtaining insights into ligand-target dissociation mechanisms. We assessed tauRAMD on a dataset of 70 diverse drug-like ligands of the N-terminal domain of HSP90alpha, a pharmaceutically important target with a highly flexible binding site, obtaining computed relative residence times with an accuracy of about 2.3tau for 78% of the compounds and less than 2.0tau within congeneric series. Analysis of dissociation trajectories reveals features that af-fect ligand unbinding rates, including transient polar interactions and steric hindrance. These results sug-gest that tauRAMD will be widely applicable as a computationally efficient aid to improving drug resi-dence times during lead optimization. | ||
| + | |||
| + | Estimation of drug-target residence times by tau -random acceleration molecular dynamics simulations.,Kokh DB, Amaral M, Bomke J, Gradler U, Musil D, Buchstaller HP, Dreyer MK, Frech M, Lowinski M, Vallee F, Bianciotto M, Rak A, Wade RC J Chem Theory Comput. 2018 May 16. doi: 10.1021/acs.jctc.8b00230. PMID:29768913<ref>PMID:29768913</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5lo5" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Amaral, M]] | [[Category: Amaral, M]] | ||
[[Category: Graedler, U]] | [[Category: Graedler, U]] | ||
[[Category: Chaperone]] | [[Category: Chaperone]] | ||
Revision as of 10:43, 12 August 2020
HSP90 WITH indole derivative
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