5u5v - Revision history

OCA at 14:25, 6 March 2024

2024-03-06T14:25:17Z

←Older revision		Revision as of 14:25, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='5u5v' size='340' side='right'caption='[[5u5v]], [[Resolution\|resolution]] 1.22Å' scene=''>		<StructureSection load='5u5v' size='340' side='right'caption='[[5u5v]], [[Resolution\|resolution]] 1.22Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u5v]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Baker's_yeast Baker's yeast~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U5V OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5U5V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u5v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_RM11-1a Saccharomyces cerevisiae RM11-1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U5V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7WA:1H-BENZIMIDAZOL-4-AMINE'>7WA</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.222Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u5u\|5u5u]], [[5u5w\|5u5w]], [[5u5x\|5u5x]], [[5u5y\|5u5y]], [[5u5z\|5u5z]], [[5u60\|5u60]], [[5u61\|5u61]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7WA:1H-BENZIMIDAZOL-4-AMINE'>7WA</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SCRG_04081 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=285006 Baker's yeast])~~</td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5u5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u5v OCA], [https://pdbe.org/5u5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u5v RCSB], [https://www.ebi.ac.uk/pdbsum/5u5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u5v 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=5u5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u5v OCA], [~~http~~://pdbe.org/5u5v PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5u5v RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5u5v PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5u5v ProSAT]</span></td></tr>	+
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/B3LRE1_YEAS1 B3LRE1_YEAS1]
-	~~Binding-site water is often displaced upon ligand recognition, but is commonly neglected in structure-based ligand discovery~~. ~~Inhomogeneous solvation theory (IST) has become popular for treating this effect, but it has not been tested in controlled experiments at atomic resolution~~. To do so, we turned to a grid-based version of this method, GIST, readily implemented in molecular docking. Whereas the term only improves docking modestly in retrospective ligand enrichment, it could be added without disrupting performance. We thus turned to prospective docking of large libraries to investigate GIST's impact on ligand discovery, geometry, and water structure in a model cavity site well-suited to exploring these terms. Although top-ranked docked molecules with and without the GIST term often overlapped, many ligands were meaningfully prioritized or deprioritized; some of these were selected for testing. Experimentally, 13/14 molecules prioritized by GIST did bind, whereas none of the molecules that it deprioritized were observed to bind. Nine crystal complexes were determined. In six, the ligand geometry corresponded to that predicted by GIST, for one of these the pose without the GIST term was wrong, and three crystallographic poses differed from both predictions. Notably, in one structure, an ordered water molecule with a high GIST displacement penalty was observed to stay in place. Inclusion of this water-displacement term can substantially improve the hit rates and ligand geometries from docking screens, although the magnitude of its effects can be small and its impact in drug binding sites merits further controlled studies.	+

-	Testing inhomogeneous solvation theory in structure-based ligand discovery.,Balius TE, Fischer M, Stein RM, Adler TB, Nguyen CN, Cruz A, Gilson MK, Kurtzman T, Shoichet BK Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):E6839-E6846. doi:, 10.1073/pnas.1703287114. Epub 2017 Jul 31. PMID:28760952<ref>PMID:28760952</ref>	+	==See Also==
-		+	*[[Cytochrome c peroxidase 3D structures\|Cytochrome c peroxidase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5u5v" style="background-color:#fffaf0;"></div>~~	+
-	== ~~References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Baker's yeast]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Fischer, M~~]]	+	[[Category: Saccharomyces cerevisiae RM11-1a]]
-	[[Category: ~~Shoichet, B K~~]]	+	[[Category: Fischer M]]
-	[[Category: ~~Cytochrome c peroxidase]]~~	+	[[Category: Shoichet BK]]
-	~~[[Category: Desolvation]]~~	+
-	~~[[Category: Docking]]~~	+
-	~~[[Category: Gist]]~~	+
-	~~[[Category: Ligand binding]]~~	+
-	~~[[Category: Model system]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 09:11, 1 January 2020

2020-01-01T09:11:05Z

←Older revision		Revision as of 09:11, 1 January 2020
Line 1:		Line 1:

	==CcP gateless cavity==		==CcP gateless cavity==
-	<StructureSection load='5u5v' size='340' side='right' caption='[[5u5v]], [[Resolution\|resolution]] 1.22Å' scene=''>	+	<StructureSection load='5u5v' size='340' side='right'caption='[[5u5v]], [[Resolution\|resolution]] 1.22Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5u5v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U5V FirstGlance]. <br>		<table><tr><td colspan='2'>[[5u5v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U5V FirstGlance]. <br>
Line 23:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Baker's yeast]]		[[Category: Baker's yeast]]
		+	[[Category: Large Structures]]
	[[Category: Fischer, M]]		[[Category: Fischer, M]]
	[[Category: Shoichet, B K]]		[[Category: Shoichet, B K]]

OCA at 19:27, 15 November 2017

2017-11-15T19:27:37Z

←Older revision		Revision as of 19:27, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='5u5v' size='340' side='right' caption='[[5u5v]], [[Resolution\|resolution]] 1.22Å' scene=''>		<StructureSection load='5u5v' size='340' side='right' caption='[[5u5v]], [[Resolution\|resolution]] 1.22Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u5v]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U5V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u5v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U5V FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7WA:1H-BENZIMIDAZOL-4-AMINE'>7WA</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7WA:1H-BENZIMIDAZOL-4-AMINE'>7WA</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u5u\|5u5u]], [[5u5w\|5u5w]], [[5u5x\|5u5x]], [[5u5y\|5u5y]], [[5u5z\|5u5z]], [[5u60\|5u60]], [[5u61\|5u61]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u5u\|5u5u]], [[5u5w\|5u5w]], [[5u5x\|5u5x]], [[5u5y\|5u5y]], [[5u5z\|5u5z]], [[5u60\|5u60]], [[5u61\|5u61]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SCRG_04081 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=285006 Baker's yeast])</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=5u5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u5v OCA], [http://pdbe.org/5u5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u5v RCSB], [http://www.ebi.ac.uk/pdbsum/5u5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u5v 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=5u5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u5v OCA], [http://pdbe.org/5u5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u5v RCSB], [http://www.ebi.ac.uk/pdbsum/5u5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u5v ProSAT]</span></td></tr>
	</table>		</table>
Line 21:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Baker's yeast]]
	[[Category: Fischer, M]]		[[Category: Fischer, M]]
	[[Category: Shoichet, B K]]		[[Category: Shoichet, B K]]

OCA at 05:56, 17 August 2017

2017-08-17T05:56:27Z

←Older revision		Revision as of 05:56, 17 August 2017
Line 10:		Line 10:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Proteins fluctuate between alternative conformations~~, ~~which presents a challenge for~~ ligand discovery ~~because such flexibility is difficult to treat computationally owing to problems with conformational sampling and energy weighting~~. ~~Here~~ we ~~describe~~ a ~~flexible docking~~ method ~~that samples~~ and ~~weights protein conformations using experimentally derived conformations as~~ a ~~guide~~. ~~The crystallographically refined occupancies~~ of these ~~conformations~~, ~~which are observable in an apo receptor structure~~, ~~define energy penalties for docking~~. In ~~a large prospective library screen~~, ~~we identified new ligands~~ that ~~target specific receptor conformations~~ of ~~a cavity in cytochrome c peroxidase~~, and ~~we confirm~~ both ~~ligand pose and associated receptor conformation~~ predictions ~~by crystallography~~. ~~The inclusion of receptor flexibility led to ligands~~ with ~~new chemotypes and physical properties~~. ~~By exploiting experimental measures~~ of ~~loop and side~~-~~chain flexibility, this method~~ can ~~be extended to~~ the ~~discovery~~ of ~~new ligands for hundreds of targets~~ in ~~the Protein Data Bank for which similar experimental information is available~~.	+	Binding-site water is often displaced upon ligand recognition, but is commonly neglected in structure-based ligand discovery. Inhomogeneous solvation theory (IST) has become popular for treating this effect, but it has not been tested in controlled experiments at atomic resolution. To do so, we turned to a grid-based version of this method, GIST, readily implemented in molecular docking. Whereas the term only improves docking modestly in retrospective ligand enrichment, it could be added without disrupting performance. We thus turned to prospective docking of large libraries to investigate GIST's impact on ligand discovery, geometry, and water structure in a model cavity site well-suited to exploring these terms. Although top-ranked docked molecules with and without the GIST term often overlapped, many ligands were meaningfully prioritized or deprioritized; some of these were selected for testing. Experimentally, 13/14 molecules prioritized by GIST did bind, whereas none of the molecules that it deprioritized were observed to bind. Nine crystal complexes were determined. In six, the ligand geometry corresponded to that predicted by GIST, for one of these the pose without the GIST term was wrong, and three crystallographic poses differed from both predictions. Notably, in one structure, an ordered water molecule with a high GIST displacement penalty was observed to stay in place. Inclusion of this water-displacement term can substantially improve the hit rates and ligand geometries from docking screens, although the magnitude of its effects can be small and its impact in drug binding sites merits further controlled studies.

-	~~Incorporation of protein flexibility and conformational energy penalties~~ in ~~docking screens to improve~~ ligand discovery.,Fischer M, ~~Coleman RG~~, ~~Fraser JS~~, Shoichet BK ~~Nat Chem~~. ~~2014 Jul~~;6(7):~~575~~-83. doi: 10.~~1038~~/~~nchem~~.~~1954~~. Epub ~~2014 May 25~~. PMID:~~24950326~~<ref>PMID:~~24950326~~</ref>	+	Testing inhomogeneous solvation theory in structure-based ligand discovery.,Balius TE, Fischer M, Stein RM, Adler TB, Nguyen CN, Cruz A, Gilson MK, Kurtzman T, Shoichet BK Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):E6839-E6846. doi:, 10.1073/pnas.1703287114. Epub 2017 Jul 31. PMID:28760952<ref>PMID:28760952</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

OCA at 17:55, 1 February 2017

2017-02-01T17:55:00Z

←Older revision		Revision as of 17:55, 1 February 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5u5v is ~~ON HOLD until Paper~~ Publication	+	==CcP gateless cavity==
		+	<StructureSection load='5u5v' size='340' side='right' caption='[[5u5v]], [[Resolution\|resolution]] 1.22Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5u5v]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U5V FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7WA:1H-BENZIMIDAZOL-4-AMINE'>7WA</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u5u\|5u5u]], [[5u5w\|5u5w]], [[5u5x\|5u5x]], [[5u5y\|5u5y]], [[5u5z\|5u5z]], [[5u60\|5u60]], [[5u61\|5u61]]</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=5u5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u5v OCA], [http://pdbe.org/5u5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u5v RCSB], [http://www.ebi.ac.uk/pdbsum/5u5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u5v ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Proteins fluctuate between alternative conformations, which presents a challenge for ligand discovery because such flexibility is difficult to treat computationally owing to problems with conformational sampling and energy weighting. Here we describe a flexible docking method that samples and weights protein conformations using experimentally derived conformations as a guide. The crystallographically refined occupancies of these conformations, which are observable in an apo receptor structure, define energy penalties for docking. In a large prospective library screen, we identified new ligands that target specific receptor conformations of a cavity in cytochrome c peroxidase, and we confirm both ligand pose and associated receptor conformation predictions by crystallography. The inclusion of receptor flexibility led to ligands with new chemotypes and physical properties. By exploiting experimental measures of loop and side-chain flexibility, this method can be extended to the discovery of new ligands for hundreds of targets in the Protein Data Bank for which similar experimental information is available.

-	~~Authors: Fischer~~, M., ~~Shoichet~~, B.K.	+	Incorporation of protein flexibility and conformational energy penalties in docking screens to improve ligand discovery.,Fischer M, Coleman RG, Fraser JS, Shoichet BK Nat Chem. 2014 Jul;6(7):575-83. doi: 10.1038/nchem.1954. Epub 2014 May 25. PMID:24950326<ref>PMID:24950326</ref>

-	~~Description: CcP gateless cavity~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5u5v" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Fischer, M]]		[[Category: Fischer, M]]
-	[[Category: Shoichet, B.K]]	+	[[Category: Shoichet, B K]]
		+	[[Category: Cytochrome c peroxidase]]
		+	[[Category: Desolvation]]
		+	[[Category: Docking]]
		+	[[Category: Gist]]
		+	[[Category: Ligand binding]]
		+	[[Category: Model system]]
		+	[[Category: Oxidoreductase]]

OCA at 20:25, 22 December 2016

2016-12-22T20:25:57Z

←Older revision		Revision as of 20:25, 22 December 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5u5v is ON HOLD	+	The entry 5u5v is ON HOLD until Paper Publication

	Authors: Fischer, M., Shoichet, B.K.		Authors: Fischer, M., Shoichet, B.K.

OCA: Protected "5u5v" [edit=sysop:move=sysop]

2016-12-15T17:43:33Z

Protected "5u5v" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:43, 15 December 2016

OCA: New page: '''Unreleased structure''' The entry 5u5v is ON HOLD Authors: Fischer, M., Shoichet, B.K. Description: CcP gateless cavity Category: Unreleased Structures Category: Fischer, M ...

2016-12-15T17:43:32Z

New page: '''Unreleased structure''' The entry 5u5v is ON HOLD Authors: Fischer, M., Shoichet, B.K. Description: CcP gateless cavity Category: Unreleased Structures Category: Fischer, M ...

New page

'''Unreleased structure'''

The entry 5u5v is ON HOLD

Authors: Fischer, M., Shoichet, B.K.

Description: CcP gateless cavity
[[Category: Unreleased Structures]]
[[Category: Fischer, M]]
[[Category: Shoichet, B.K]]