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 with sequence from [ | <table><tr><td colspan='2'>[[6elp]] 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=6ELP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ELP FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6elp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6elp OCA], [https://pdbe.org/6elp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6elp RCSB], [https://www.ebi.ac.uk/pdbsum/6elp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6elp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Eggenweiler | [[Category: Eggenweiler H-M]] | ||
[[Category: Lehmann | [[Category: Lehmann M]] | ||
[[Category: Musil | [[Category: Musil D]] | ||
Latest revision as of 15:19, 9 May 2024
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
FunctionHS90A_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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