6elp: Difference between revisions
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<StructureSection load='6elp' size='340' side='right' caption='[[6elp]], [[Resolution|resolution]] 1.85Å' scene=''> | <StructureSection load='6elp' size='340' side='right' caption='[[6elp]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6elp]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ELP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ELP FirstGlance]. <br> | <table><tr><td colspan='2'>[[6elp]] 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=6ELP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ELP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BA8:4-[2-(2-chlorophenyl)pyrazol-3-yl]-6-(2-pyridin-2-ylethyl)benzene-1,3-diol'>BA8</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BA8:4-[2-(2-chlorophenyl)pyrazol-3-yl]-6-(2-pyridin-2-ylethyl)benzene-1,3-diol'>BA8</scene></td></tr> | ||
<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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6elp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6elp OCA], [http://pdbe.org/6elp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6elp RCSB], [http://www.ebi.ac.uk/pdbsum/6elp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6elp ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6elp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6elp OCA], [http://pdbe.org/6elp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6elp RCSB], [http://www.ebi.ac.uk/pdbsum/6elp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6elp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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</div> | </div> | ||
<div class="pdbe-citations 6elp" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6elp" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Heat Shock Proteins|Heat Shock Proteins]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Eggenweiler, H M]] | [[Category: Eggenweiler, H M]] | ||
[[Category: Lehmann, M]] | [[Category: Lehmann, M]] |
Revision as of 12:47, 18 July 2018
Estimation of relative drug-target residence times by random acceleration molecular dynamics simulationEstimation of relative drug-target residence times by random acceleration molecular dynamics simulation
Structural highlights
Function[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.[1] [2] Publication Abstract from PubMedDrug-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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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