3fc1: Difference between revisions
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[[Image: | ==Crystal structure of p38 kinase bound to pyrimido-pyridazinone inhibitor== | ||
<StructureSection load='3fc1' size='340' side='right' caption='[[3fc1]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3fc1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FC1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FC1 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=52P:5-(2,6-DICHLOROPHENYL)-2-[(2,4-DIFLUOROPHENYL)SULFANYL]-6H-PYRIMIDO[1,6-B]PYRIDAZIN-6-ONE'>52P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fc1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fc1 RCSB], [http://www.ebi.ac.uk/pdbsum/3fc1 PDBsum]</span></td></tr> | |||
<table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fc/3fc1_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The recently described molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method for calculating free energies is applied to a congeneric series of 16 ligands to p38 MAP kinase whose binding constants span approximately 2 orders of magnitude. These compounds have previously been used to test and compare other free energy calculation methods, including thermodynamic integration (TI), OWFEG, ChemScore, PLPScore, and Dock Energy Score. We find that the MM-PBSA performs relatively poorly for this set of ligands, yielding results much inferior to those from TI or OWFEG, inferior to Dock Energy Score, and not appreciably better than ChemScore or PLPScore but at an appreciably larger computational cost than any of these other methods. This suggests that one should be selective in applying the MM-PBSA method and that for systems that are amenable to other free energy approaches, these other approaches may be preferred. We also examine the single simulation approximation for MM-PBSA, whereby the required ligand and protein trajectories are extracted from a single MD simulation rather than two separate MD runs. This assumption, sometimes used to speed the MM-PBSA calculation, is found to yield significantly inferior results with only a moderate net percentage reduction in total simulation time. | |||
Evaluating the molecular mechanics poisson-boltzmann surface area free energy method using a congeneric series of ligands to p38 MAP kinase.,Pearlman DA J Med Chem. 2005 Dec 1;48(24):7796-807. PMID:16302819<ref>PMID:16302819</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]] | *[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mitogen-activated protein kinase]] | [[Category: Mitogen-activated protein kinase]] | ||
Revision as of 16:22, 29 September 2014
Crystal structure of p38 kinase bound to pyrimido-pyridazinone inhibitorCrystal structure of p38 kinase bound to pyrimido-pyridazinone inhibitor
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe recently described molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method for calculating free energies is applied to a congeneric series of 16 ligands to p38 MAP kinase whose binding constants span approximately 2 orders of magnitude. These compounds have previously been used to test and compare other free energy calculation methods, including thermodynamic integration (TI), OWFEG, ChemScore, PLPScore, and Dock Energy Score. We find that the MM-PBSA performs relatively poorly for this set of ligands, yielding results much inferior to those from TI or OWFEG, inferior to Dock Energy Score, and not appreciably better than ChemScore or PLPScore but at an appreciably larger computational cost than any of these other methods. This suggests that one should be selective in applying the MM-PBSA method and that for systems that are amenable to other free energy approaches, these other approaches may be preferred. We also examine the single simulation approximation for MM-PBSA, whereby the required ligand and protein trajectories are extracted from a single MD simulation rather than two separate MD runs. This assumption, sometimes used to speed the MM-PBSA calculation, is found to yield significantly inferior results with only a moderate net percentage reduction in total simulation time. Evaluating the molecular mechanics poisson-boltzmann surface area free energy method using a congeneric series of ligands to p38 MAP kinase.,Pearlman DA J Med Chem. 2005 Dec 1;48(24):7796-807. PMID:16302819[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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