6ey9: Difference between revisions

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-'''Unreleased structure'''
-The entry 6ey9 is ON HOLD
+==Estimation of relative drug-target residence times by random acceleration molecular dynamics simulation==
+<StructureSection load='6ey9' size='340' side='right' caption='[[6ey9]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ey9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EY9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EY9 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C4N:~{N}-[(4-chlorophenyl)methyl]-~{N}-methyl-3-[(3-methylphenyl)methyl]-6-oxidanyl-1~{H}-indazole-5-carboxamide'>C4N</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ey9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ey9 OCA], [http://pdbe.org/6ey9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ey9 RCSB], [http://www.ebi.ac.uk/pdbsum/6ey9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ey9 ProSAT]</span></td></tr>
+</table>
+== 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>
+<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.
-Authors: Musil, D., Lehmann, M., Buchstaller, H.-P.
+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>
-Description: Estimation of relative drug-target residence times by random acceleration molecular dynamics simulation
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6ey9" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Buchstaller, H P]]
 [[Category: Lehmann, M]]
-[[Category: Buchstaller, H.-P]]
 [[Category: Musil, D]]
+[[Category: Atp binding]]
+[[Category: Chaperone]]
+[[Category: Chaperone protein]]