8pkw - Revision history

OCA at 11:13, 22 November 2023

OCA — Wed, 22 Nov 2023 11:13:56 GMT

←Older revision		Revision as of 11:13, 22 November 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8pkw is ~~ON HOLD until Paper~~ Publication	+	==Kelch domain of KEAP1 in complex with a ortho-dimethylbenzene linked cyclic peptide 5 (ortho-WRCDEETGEC)==
		+	<StructureSection load='8pkw' size='340' side='right'caption='[[8pkw]], [[Resolution\|resolution]] 1.54Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8pkw]] is a 3 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=8PKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PKW FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.54Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZK2:(2-methylphenyl)methanol'>ZK2</scene></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=8pkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pkw OCA], [https://pdbe.org/8pkw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pkw RCSB], [https://www.ebi.ac.uk/pdbsum/8pkw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pkw ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Nrf2 transcription factor is a master regulator of the cellular response to oxidative stress, and Keap1 is its primary negative regulator. Activating Nrf2 by inhibiting the Nrf2-Keap1 protein-protein interaction has shown promise for treating cancer and inflammatory diseases. A loop derived from Nrf2 has been shown to inhibit Keap1 selectively, especially when cyclized, but there are no reliable design methods for predicting an optimal macrocyclization strategy. In this work, we employed all-atom, explicit-solvent molecular dynamics simulations with enhanced sampling methods to predict the relative degree of preorganization for a series of peptides cyclized with a set of bis-thioether "staples". We then correlated these predictions to experimentally measured binding affinities for Keap1 and crystal structures of the cyclic peptides bound to Keap1. This work showcases a computational method for designing cyclic peptides by simulating and comparing their entire solution-phase ensembles, providing key insights into designing cyclic peptides as selective inhibitors of protein-protein interactions.

-	~~Authors~~:	+	Computational Prediction of Cyclic Peptide Structural Ensembles and Application to the Design of Keap1 Binders.,Fonseca Lopez F, Miao J, Damjanovic J, Bischof L, Braun MB, Ling Y, Hartmann MD, Lin YS, Kritzer JA J Chem Inf Model. 2023 Nov 13;63(21):6925-6937. doi: 10.1021/acs.jcim.3c01337. , Epub 2023 Nov 2. PMID:37917529<ref>PMID:37917529</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8pkw" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Bischof L]]
		+	[[Category: Braun MB]]
		+	[[Category: Hartmann MD]]

OCA: Replacing page with ''''Unreleased structure''' The entry 8pkw is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures'

OCA — Wed, 22 Nov 2023 05:38:08 GMT

Replacing page with ''''Unreleased structure''' The entry 8pkw is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures'

←Older revision		Revision as of 05:38, 22 November 2023
Line 1:		Line 1:
		+	'''Unreleased structure'''

-	~~==Kelch domain of KEAP1 in complex with a ortho-dimethylbenzene linked cyclic peptide 5 (ortho-WRCDEETGEC)==~~	+	The entry 8pkw is ON HOLD until Paper Publication
-	~~<StructureSection load='~~8pkw~~' size='340' side='right'caption='[[8pkw]], [[Resolution\|resolution]] 1.54Å' scene=''>~~	+
-	~~== Structural highlights ==~~	+
-	~~<table><tr><td colspan='2'>[[8pkw]]~~ is a 3 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=8PKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PKW FirstGlance]. <br>	+
-	~~</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.54Å</td></tr>~~	+
-	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZK2:(2-methylphenyl)methanol'>ZK2</scene></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=8pkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pkw OCA], [https://pdbe.org/8pkw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pkw RCSB], [https://www.ebi.ac.uk/pdbsum/8pkw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pkw ProSAT]</span></td></tr>	+
-	~~</table>~~	+
-	~~== Function ==~~	+
-	~~[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN]~~	+
-	~~<div style="background-color:#fffaf0;">~~	+
-	== Publication ~~Abstract from PubMed ==~~	+
-	The Nrf2 transcription factor is a master regulator of the cellular response to oxidative stress, and Keap1 is its primary negative regulator. Activating Nrf2 by inhibiting the Nrf2-Keap1 protein-protein interaction has shown promise for treating cancer and inflammatory diseases. A loop derived from Nrf2 has been shown to inhibit Keap1 selectively, especially when cyclized, but there are no reliable design methods for predicting an optimal macrocyclization strategy. In this work, we employed all-atom, explicit-solvent molecular dynamics simulations with enhanced sampling methods to predict the relative degree of preorganization for a series of peptides cyclized with a set of bis-thioether "staples". We then correlated these predictions to experimentally measured binding affinities for Keap1 and crystal structures of the cyclic peptides bound to Keap1. This work showcases a computational method for designing cyclic peptides by simulating and comparing their entire solution-phase ensembles, providing key insights into designing cyclic peptides as selective inhibitors of protein-protein interactions.	+

-	Computational Prediction of Cyclic Peptide Structural Ensembles and Application to the Design of Keap1 Binders.,Fonseca Lopez F, Miao J, Damjanovic J, Bischof L, Braun MB, Ling Y, Hartmann MD, Lin YS, Kritzer JA J Chem Inf Model. 2023 Nov 13;63(21):~~6925-6937. doi: 10.1021/acs.jcim.3c01337. , Epub 2023 Nov 2. PMID:37917529<ref>PMID:37917529</ref>~~	+	Authors:

-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+	Description:
-	~~</div>~~	+	[[Category: Unreleased Structures]]
-	~~<div class="pdbe-citations 8pkw" style="background-color~~:~~#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
-	~~__TOC__~~	+
-	~~</StructureSection>~~	+
-	[[Category: ~~Homo sapiens]]~~	+
-	~~[[Category: Large~~ Structures]]	+
-	~~[[Category: Bischof L]]~~	+
-	~~[[Category: Braun MB]]~~	+
-	~~[[Category: Hartmann MD~~]]	+

OCA at 07:40, 15 November 2023

OCA — Wed, 15 Nov 2023 07:40:01 GMT

←Older revision		Revision as of 07:40, 15 November 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8pkw is ~~ON HOLD until Paper~~ Publication	+	==Kelch domain of KEAP1 in complex with a ortho-dimethylbenzene linked cyclic peptide 5 (ortho-WRCDEETGEC)==
		+	<StructureSection load='8pkw' size='340' side='right'caption='[[8pkw]], [[Resolution\|resolution]] 1.54Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8pkw]] is a 3 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=8PKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PKW FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.54Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZK2:(2-methylphenyl)methanol'>ZK2</scene></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=8pkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pkw OCA], [https://pdbe.org/8pkw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pkw RCSB], [https://www.ebi.ac.uk/pdbsum/8pkw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pkw ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Nrf2 transcription factor is a master regulator of the cellular response to oxidative stress, and Keap1 is its primary negative regulator. Activating Nrf2 by inhibiting the Nrf2-Keap1 protein-protein interaction has shown promise for treating cancer and inflammatory diseases. A loop derived from Nrf2 has been shown to inhibit Keap1 selectively, especially when cyclized, but there are no reliable design methods for predicting an optimal macrocyclization strategy. In this work, we employed all-atom, explicit-solvent molecular dynamics simulations with enhanced sampling methods to predict the relative degree of preorganization for a series of peptides cyclized with a set of bis-thioether "staples". We then correlated these predictions to experimentally measured binding affinities for Keap1 and crystal structures of the cyclic peptides bound to Keap1. This work showcases a computational method for designing cyclic peptides by simulating and comparing their entire solution-phase ensembles, providing key insights into designing cyclic peptides as selective inhibitors of protein-protein interactions.

-	~~Authors~~:	+	Computational Prediction of Cyclic Peptide Structural Ensembles and Application to the Design of Keap1 Binders.,Fonseca Lopez F, Miao J, Damjanovic J, Bischof L, Braun MB, Ling Y, Hartmann MD, Lin YS, Kritzer JA J Chem Inf Model. 2023 Nov 13;63(21):6925-6937. doi: 10.1021/acs.jcim.3c01337. , Epub 2023 Nov 2. PMID:37917529<ref>PMID:37917529</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8pkw" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Bischof L]]
		+	[[Category: Braun MB]]
		+	[[Category: Hartmann MD]]

OCA at 09:03, 2 August 2023

OCA — Wed, 02 Aug 2023 09:03:59 GMT

←Older revision		Revision as of 09:03, 2 August 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8pkw is ON HOLD	+	The entry 8pkw is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8pkw" [edit=sysop:move=sysop]

OCA — Wed, 05 Jul 2023 04:16:26 GMT

Protected "8pkw" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:16, 5 July 2023

OCA: New page: '''Unreleased structure''' The entry 8pkw is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 05 Jul 2023 04:16:25 GMT

New page: '''Unreleased structure''' The entry 8pkw is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8pkw is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]