6vlv: Difference between revisions

Latest revision as of 13:13, 6 November 2024

Factor XIa in complex with compound 11

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.72Å
Ligands:	FLC, R3A
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Two orthogonal approaches for hit identification in drug discovery are large-scale in vitro and in silico screening. In recent years, due to the emergence of new targets and a rapid increase in the size of the readily synthesizable chemical space, there is a growing emphasis on the integration of the two techniques to improve the hit finding efficiency. Here, we highlight three examples of drug discovery projects at Merck & Co., Inc., Kenilworth, NJ, USA in which different virtual screening (VS) techniques, each specifically tailored to leverage knowledge available for the target, were utilized to augment the selection of high-quality chemical matter for in vitro assays and to enhance the diversity and tractability of hits. Central to success is a fully integrated workflow combining in silico and experimental expertise at every stage of the hit identification process. We advocate that workflows encompassing VS as part of an integrated hit finding plan should be widely adopted to accelerate hit identification and foster cross-functional collaborations in modern drug discovery.

Augmenting Hit Identification by Virtual Screening Techniques in Small Molecule Drug Discovery.,Yan XC, Sanders JM, Gao YD, Tudor M, Haidle AM, Klein DJ, Converso A, Lesburg CA, Zang Y, Wood HB J Chem Inf Model. 2020 May 1. doi: 10.1021/acs.jcim.0c00113. PMID:32309939^[1]

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

References

↑ Yan XC, Sanders JM, Gao YD, Tudor M, Haidle AM, Klein DJ, Converso A, Lesburg CA, Zang Y, Wood HB. Augmenting Hit Identification by Virtual Screening Techniques in Small Molecule Drug Discovery. J Chem Inf Model. 2020 May 1. doi: 10.1021/acs.jcim.0c00113. PMID:32309939 doi:https://dx.doi.org/10.1021/acs.jcim.0c00113

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Yan XC, Sanders JM, Gao YD, Tudor M, Haidle AM, Klein DJ, Converso A, Lesburg CA, Zang Y, Wood HB. Augmenting Hit Identification by Virtual Screening Techniques in Small Molecule Drug Discovery. J Chem Inf Model. 2020 May 1. doi: 10.1021/acs.jcim.0c00113. PMID:32309939 doi:https://dx.doi.org/10.1021/acs.jcim.0c00113

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='6vlv' size='340' side='right'caption='[[6vlv]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6vlv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VLV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VLV FirstGlance]. <br>
+<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VLV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VLV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=R3A:1-carbamimidamido-4-chloro-N-[(2R)-3-methyl-1-(morpholin-4-yl)-1-oxobutan-2-yl]isoquinoline-7-sulfonamide'>R3A</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]] 1.72&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=R3A:1-carbamimidamido-4-chloro-N-[(2R)-3-methyl-1-(morpholin-4-yl)-1-oxobutan-2-yl]isoquinoline-7-sulfonamide'>R3A</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=6vlv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vlv OCA], [https://pdbe.org/6vlv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vlv RCSB], [https://www.ebi.ac.uk/pdbsum/6vlv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vlv ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vlv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vlv OCA], [http://pdbe.org/6vlv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vlv RCSB], [http://www.ebi.ac.uk/pdbsum/6vlv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vlv ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[http://omim.org/entry/612416 612416]]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>
-== Function ==
-[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 19: @@
 ==See Also==
-*[[Factor XIa|Factor XIa]]
+*[[Factor XIa 3D structures|Factor XIa 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Coagulation factor XIa]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Lesburg, C A]]
+[[Category: Lesburg CA]]
-[[Category: Blood clotting]]
-[[Category: Coagulation factor]]
-[[Category: Hydrolase]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Serine protease]]

6vlv: Difference between revisions

Latest revision as of 13:13, 6 November 2024

Factor XIa in complex with compound 11

Structural highlights

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools