5seq - Revision history

OCA at 07:30, 17 October 2024

2024-10-17T07:30:36Z

← Older revision		Revision as of 07:30, 17 October 2024
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	==~~Crystal Structure of human phosphodiesterase~~ 10 ~~in complex with 5,6,8-trimethyl-2-[2-~~(~~2-methyl-5-pyrrolidin-1-yl-1,2,4-triazol-3-yl~~)~~ethyl]-[1,2,4]triazolo[1~~,~~5-a]pyrazine~~==		==CRYSTAL STRUCTURE OF HUMAN PHOSPHODIESTERASE 10 IN COMPLEX WITH c1(nn(c(n1)CCc2nn3c(n2)c(nc(c3C)C)C)C)N4CCCC4, micromolar IC50=0.037262==
	<StructureSection load='5seq' size='340' side='right'caption='[[5seq]], [[Resolution\|resolution]] 2.18Å' scene=''>		<StructureSection load='5seq' size='340' side='right'caption='[[5seq]], [[Resolution\|resolution]] 2.18Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>		[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			We release a new, high quality data set of 1162 PDE10A inhibitors with experimentally determined binding affinities together with 77 PDE10A X-ray co-crystal structures from a Roche legacy project. This data set is used to compare the performance of different 2D- and 3D-machine learning (ML) as well as empirical scoring functions for predicting binding affinities with high throughput. We simulate use cases that are relevant in the lead optimization phase of early drug discovery. ML methods perform well at interpolation, but poorly in extrapolation scenarios-which are most relevant to a real-world application. Moreover, we find that investing into the docking workflow for binding pose generation using multi-template docking is rewarded with an improved scoring performance. A combination of 2D-ML and 3D scoring using a modified piecewise linear potential shows best overall performance, combining information on the protein environment with learning from existing SAR data.

			A high quality, industrial data set for binding affinity prediction: performance comparison in different early drug discovery scenarios.,Tosstorff A, Rudolph MG, Cole JC, Reutlinger M, Kramer C, Schaffhauser H, Nilly A, Flohr A, Kuhn B J Comput Aided Mol Des. 2022 Oct;36(10):753-765. doi: 10.1007/s10822-022-00478-x. , Epub 2022 Sep 25. PMID:36153472<ref>PMID:36153472</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 5seq" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:57, 3 April 2024

2024-04-03T06:57:46Z

← Older revision		Revision as of 06:57, 3 April 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5seq]] is a 4 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=5SEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SEQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[5seq]] is a 4 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=5SEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SEQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=IGO:(4S)-5,6,8-trimethyl-2-{2-[1-methyl-3-(pyrrolidin-1-yl)-1H-1,2,4-triazol-5-yl]ethyl}[1,2,4]triazolo[1,5-a]pyrazine'>IGO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.18Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=IGO:(4S)-5,6,8-trimethyl-2-{2-[1-methyl-3-(pyrrolidin-1-yl)-1H-1,2,4-triazol-5-yl]ethyl}[1,2,4]triazolo[1,5-a]pyrazine'>IGO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5seq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5seq OCA], [https://pdbe.org/5seq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5seq RCSB], [https://www.ebi.ac.uk/pdbsum/5seq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5seq ProSAT]</span></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=5seq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5seq OCA], [https://pdbe.org/5seq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5seq RCSB], [https://www.ebi.ac.uk/pdbsum/5seq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5seq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>		[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	We release a new, high quality data set of 1162 PDE10A inhibitors with experimentally determined binding affinities together with 77 PDE10A X-ray co-crystal structures from a Roche legacy project. This data set is used to compare the performance of different 2D- and 3D-machine learning (ML) as well as empirical scoring functions for predicting binding affinities with high throughput. We simulate use cases that are relevant in the lead optimization phase of early drug discovery. ML methods perform well at interpolation, but poorly in extrapolation scenarios-which are most relevant to a real-world application. Moreover, we find that investing into the docking workflow for binding pose generation using multi-template docking is rewarded with an improved scoring performance. A combination of 2D-ML and 3D scoring using a modified piecewise linear potential shows best overall performance, combining information on the protein environment with learning from existing SAR data.

	A high quality, industrial data set for binding affinity prediction: performance comparison in different early drug discovery scenarios.,Tosstorff A, Rudolph MG, Cole JC, Reutlinger M, Kramer C, Schaffhauser H, Nilly A, Flohr A, Kuhn B J Comput Aided Mol Des. 2022 Oct;36(10):753-765. doi: 10.1007/s10822-022-00478-x., Epub 2022 Sep 25. PMID:36153472<ref>PMID:36153472</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 5seq" style="background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:29, 3 November 2022

2022-11-03T07:29:33Z

@@ Line 1: / Line 1: @@
-The entry 5seq is ON HOLD  until 2024-01-21
+==Crystal Structure of human phosphodiesterase 10 in complex with 5,6,8-trimethyl-2-[2-(2-methyl-5-pyrrolidin-1-yl-1,2,4-triazol-3-yl)ethyl]-[1,2,4]triazolo[1,5-a]pyrazine==
-Authors:
+A high quality, industrial data set for binding affinity prediction: performance comparison in different early drug discovery scenarios.,Tosstorff A, Rudolph MG, Cole JC, Reutlinger M, Kramer C, Schaffhauser H, Nilly A, Flohr A, Kuhn B J Comput Aided Mol Des. 2022 Oct;36(10):753-765. doi: 10.1007/s10822-022-00478-x., Epub 2022 Sep 25. PMID:36153472<ref>PMID:36153472</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>

OCA at 05:54, 22 June 2022

2022-06-22T05:54:02Z

← Older revision		Revision as of 05:54, 22 June 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 5seq is ON HOLD until ~~Jan~~ 21 ~~2024~~		The entry 5seq is ON HOLD until 2024-01-21

	Authors:		Authors:

OCA at 05:52, 9 February 2022

2022-02-09T05:52:13Z

← Older revision		Revision as of 05:52, 9 February 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 5seq is ON HOLD		The entry 5seq is ON HOLD until Jan 21 2024

	Authors:		Authors:

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

2022-02-02T05:20:16Z

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

← Older revision	Revision as of 05:20, 2 February 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5seq is ON HOLD Authors: Description: Category: Unreleased Structures

2022-02-02T05:20:15Z

New page: '''Unreleased structure''' The entry 5seq is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5seq is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]