Induced fit in liver X receptor beta: A molecular dynamics‐based investigation
Identifieur interne : 001E26 ( Istex/Corpus ); précédent : 001E25; suivant : 001E27Induced fit in liver X receptor beta: A molecular dynamics‐based investigation
Auteurs : Alexandre Beautrait ; Arnaud S. Karaboga ; Michel Souchet ; Bernard MaigretSource :
- Proteins: Structure, Function, and Bioinformatics [ 0887-3585 ] ; 2008-08-15.
English descriptors
- Teeft :
- Acidic group, Acidic moiety, Activation function, Activation helix, Active conformation, Agonist, Average distance, Average rmsd, Average rmsd value, Binding domain, Binding pocket, Biol, Biol chem, Bisphenyl group, Bisphenyl moiety, Campus scientifique, Carboxylate moiety, Chem, Color figure, Complexed, Comput chem, Conformation, Crucial role, Crystal structure, Crystal structures, Different shapes, Drug design, Dynamics, Electrostatic interaction, Equilibration phase, Extreme shapes, Groupe orpailleur, Helix, Hydrophobic, Interaction energy, Laboratoires fournier, Ligand, Ligand binding, Ligand binding domain, Ligand binding pocket, Lxrb, Lxrb complexed, Lxrb lbds complexed, Moiety, Molecular dynamics, Molecular dynamics simulations, Molecular dynamics study, Nuclear receptor, Nuclear receptors, Online, Online issue, Phenylsulfonyl group, Phenylsulfonyl moiety, Phys chem, Polar residues, Present study, Protonation, Protonation state, Receptor, Receptor beta, Reference system, Reference systems, Residue, Respective ligand, Salt bridge, Sbdd strategy, Side chain, Simulation, Solvay pharmaceuticals company, Structural analysis, Synthetic ligands, Trajectory, Water molecule, Water molecules.
Abstract
Ligand induced fit phenomenon occurring at the ligand binding domain of the liver X receptor beta (LXRβ) was investigated by means of molecular dynamics. Reliability of a 4‐ns trajectory was tested from two distinct LXRβ crystal complexes 1PQ6B/GW and 1PQ9B/T09 characterized by an open and a closed state of the pocket, respectively. Crossed complexes 1PQ6B/T09 and 1PQ9B/GW were then submitted to the same molecular dynamic conditions, which were able to recover LXRβ conformations similar to the original crystallography data. Analysis of “open to closed” and “closed to open” conformational transitions pointed out the dynamic role of critical residues lining the ligand binding pocket involved in the local remodeling upon ligand binding (e.g., Phe271, Phe329, Phe340, Arg319, Glu281). Altogether, the present study indicates that the molecular dynamic protocol is a consistent approach for managing LXRβ‐related induced fit process. This protocol could therefore be used for refining ligand docking solutions of a structure‐based design strategy. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/prot.21977
Links to Exploration step
ISTEX:826C476329C9B8BD122A2ACB403ADC4936D98858Le document en format XML
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Reliability of a 4‐ns trajectory was tested from two distinct LXRβ crystal complexes 1PQ6B/GW and 1PQ9B/T09 characterized by an open and a closed state of the pocket, respectively. Crossed complexes 1PQ6B/T09 and 1PQ9B/GW were then submitted to the same molecular dynamic conditions, which were able to recover LXRβ conformations similar to the original crystallography data. Analysis of “open to closed” and “closed to open” conformational transitions pointed out the dynamic role of critical residues lining the ligand binding pocket involved in the local remodeling upon ligand binding (e.g., Phe271, Phe329, Phe340, Arg319, Glu281). Altogether, the present study indicates that the molecular dynamic protocol is a consistent approach for managing LXRβ‐related induced fit process. This protocol could therefore be used for refining ligand docking solutions of a structure‐based design strategy. 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Karaboga contributed equally to this work.</note></author><author xml:id="author-0001"><persName><forename type="first">Arnaud S.</forename><surname>Karaboga</surname></persName><affiliation><orgName type="laboratory">Laboratoires Fournier</orgName><address><addrLine>a Solvay Pharmaceuticals company</addrLine><addrLine>50 rue de Dijon</addrLine><addrLine>21121 Daix</addrLine><country key="FR">FRANCE</country><country key="FR"></country></address></affiliation><note type="foot">Alexandre Beautrait and Arnaud S. Karaboga contributed equally to this work.</note></author><author xml:id="author-0002" role="corresp"><persName><forename type="first">Michel</forename><surname>Souchet</surname></persName><email>michel.souchet@solvay.com</email><affiliation><orgName type="laboratory">Laboratoires Fournier</orgName><address><addrLine>a Solvay Pharmaceuticals company</addrLine><addrLine>50 rue de Dijon</addrLine><addrLine>21121 Daix</addrLine><country key="FR">FRANCE</country><country key="FR"></country></address></affiliation><affiliation>Michel Souchet, Laboratoires Fournier, a Solvay Pharmaceuticals Company, 50 rue de Dijon, 21121 Daix, France=== Bernard Maigret, Nancy‐Université, groupe ORPAILLEUR, UMR CNRS/UHP 7503, LORIA, Campus scientifique, BP239, 54506 Vandœuvre‐lès‐Nancy Cedex, France===</affiliation></author><author xml:id="author-0003" role="corresp"><persName><forename type="first">Bernard</forename><surname>Maigret</surname></persName><email>bernard.maigret@loria.fr</email><affiliation><orgName type="institution">Nancy‐Université</orgName><address><addrLine>groupe ORPAILLEUR</addrLine><addrLine>UMR CNRS/UHP 7503</addrLine><addrLine>LORIA</addrLine><addrLine>Campus scientifique</addrLine><addrLine>BP239</addrLine><addrLine>54506 Vandœuvre‐lès‐Nancy Cedex</addrLine><country key="FR">FRANCE</country><country key="FR"></country></address></affiliation><affiliation>Michel Souchet, Laboratoires Fournier, a Solvay Pharmaceuticals Company, 50 rue de Dijon, 21121 Daix, France=== Bernard Maigret, Nancy‐Université, groupe ORPAILLEUR, UMR CNRS/UHP 7503, LORIA, Campus scientifique, BP239, 54506 Vandœuvre‐lès‐Nancy Cedex, France===</affiliation></author><idno type="istex">826C476329C9B8BD122A2ACB403ADC4936D98858</idno><idno type="ark">ark:/67375/WNG-1GHF12RV-X</idno><idno type="DOI">10.1002/prot.21977</idno><idno type="unit">PROT21977</idno><idno type="toTypesetVersion">file:PROT.PROT21977.pdf</idno></analytic><monogr><title level="j" type="main">Proteins: Structure, Function, and Bioinformatics</title><title level="j" type="alt">PROTEINS: STRUCTURE, FUNCTION, AND BIOINFORMATICS</title><idno type="pISSN">0887-3585</idno><idno type="eISSN">1097-0134</idno><idno type="book-DOI">10.1002/(ISSN)1097-0134</idno><idno type="book-part-DOI">10.1002/prot.v72:3</idno><idno type="product">PROT</idno><imprint><biblScope unit="vol">72</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="873">873</biblScope><biblScope unit="page" to="882">882</biblScope><biblScope unit="page-count">10</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2008-08-15"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>Ligand induced fit phenomenon occurring at the ligand binding domain of the liver X receptor beta (LXRβ) was investigated by means of molecular dynamics. 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Reliability of a 4‐ns trajectory was tested from two distinct LXRβ crystal complexes 1PQ6B/GW and 1PQ9B/T09 characterized by an open and a closed state of the pocket, respectively. Crossed complexes 1PQ6B/T09 and 1PQ9B/GW were then submitted to the same molecular dynamic conditions, which were able to recover LXRβ conformations similar to the original crystallography data. Analysis of “open to closed” and “closed to open” conformational transitions pointed out the dynamic role of critical residues lining the ligand binding pocket involved in the local remodeling upon ligand binding (e.g., Phe271, Phe329, Phe340, Arg319, Glu281). Altogether, the present study indicates that the molecular dynamic protocol is a consistent approach for managing LXRβ‐related induced fit process. This protocol could therefore be used for refining ligand docking solutions of a structure‐based design strategy. Proteins 2008. © 2008 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Alexandre Beautrait and Arnaud S. Karaboga contributed equally to this work.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Induced fit in liver X receptor beta: A molecular dynamics‐based investigation</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Investigation of the LXRβ‐Induced Fit by MD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Induced fit in liver X receptor beta: A molecular dynamics‐based investigation</title></titleInfo><name type="personal"><namePart type="given">Alexandre</namePart><namePart type="family">Beautrait</namePart><affiliation>Nancy‐Université, groupe ORPAILLEUR, UMR CNRS/UHP 7503, LORIA, Campus scientifique, BP239, 54506 Vandœuvre‐lès‐Nancy Cedex, France</affiliation><description>Alexandre Beautrait and Arnaud S. Karaboga contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Arnaud S.</namePart><namePart type="family">Karaboga</namePart><affiliation>Laboratoires Fournier, a Solvay Pharmaceuticals company, 50 rue de Dijon, 21121 Daix, France</affiliation><description>Alexandre Beautrait and Arnaud S. Karaboga contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michel</namePart><namePart type="family">Souchet</namePart><affiliation>Laboratoires Fournier, a Solvay Pharmaceuticals company, 50 rue de Dijon, 21121 Daix, France</affiliation><affiliation>E-mail: michel.souchet@solvay.com</affiliation><affiliation>Michel Souchet, Laboratoires Fournier, a Solvay Pharmaceuticals Company, 50 rue de Dijon, 21121 Daix, France===Bernard Maigret, Nancy‐Université, groupe ORPAILLEUR, UMR CNRS/UHP 7503, LORIA, Campus scientifique, BP239, 54506 Vandœuvre‐lès‐Nancy Cedex, France===</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bernard</namePart><namePart type="family">Maigret</namePart><affiliation>Nancy‐Université, groupe ORPAILLEUR, UMR CNRS/UHP 7503, LORIA, Campus scientifique, BP239, 54506 Vandœuvre‐lès‐Nancy Cedex, France</affiliation><affiliation>E-mail: bernard.maigret@loria.fr</affiliation><affiliation>Michel Souchet, Laboratoires Fournier, a Solvay Pharmaceuticals Company, 50 rue de Dijon, 21121 Daix, France===Bernard Maigret, Nancy‐Université, groupe ORPAILLEUR, UMR CNRS/UHP 7503, LORIA, Campus scientifique, BP239, 54506 Vandœuvre‐lès‐Nancy Cedex, France===</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2008-08-15</dateIssued><dateCaptured encoding="w3cdtf">2007-10-26</dateCaptured><dateValid encoding="w3cdtf">2007-12-20</dateValid><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">9</extent><extent unit="tables">0</extent><extent unit="references">42</extent><extent unit="words">6047</extent></physicalDescription><abstract lang="en">Ligand induced fit phenomenon occurring at the ligand binding domain of the liver X receptor beta (LXRβ) was investigated by means of molecular dynamics. Reliability of a 4‐ns trajectory was tested from two distinct LXRβ crystal complexes 1PQ6B/GW and 1PQ9B/T09 characterized by an open and a closed state of the pocket, respectively. Crossed complexes 1PQ6B/T09 and 1PQ9B/GW were then submitted to the same molecular dynamic conditions, which were able to recover LXRβ conformations similar to the original crystallography data. Analysis of “open to closed” and “closed to open” conformational transitions pointed out the dynamic role of critical residues lining the ligand binding pocket involved in the local remodeling upon ligand binding (e.g., Phe271, Phe329, Phe340, Arg319, Glu281). Altogether, the present study indicates that the molecular dynamic protocol is a consistent approach for managing LXRβ‐related induced fit process. This protocol could therefore be used for refining ligand docking solutions of a structure‐based design strategy. Proteins 2008. © 2008 Wiley‐Liss, Inc.</abstract><note type="funding">Association pour la Recherche sur le Cancer (ARC) - No. JR/MLD/MDV‐A06/4; </note><subject lang="en"><genre>keywords</genre><topic>induced fit</topic><topic>liver X receptor</topic><topic>molecular dynamics</topic><topic>protein flexibility</topic><topic>structure‐based drug design</topic></subject><relatedItem type="host"><titleInfo><title>Proteins: Structure, Function, and Bioinformatics</title></titleInfo><titleInfo type="abbreviated"><title>Proteins</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><subject><genre>article-category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0887-3585</identifier><identifier type="eISSN">1097-0134</identifier><identifier type="DOI">10.1002/(ISSN)1097-0134</identifier><identifier type="PublisherID">PROT</identifier><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>72</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>873</start><end>882</end><total>10</total></extent></part></relatedItem><identifier type="istex">826C476329C9B8BD122A2ACB403ADC4936D98858</identifier><identifier type="ark">ark:/67375/WNG-1GHF12RV-X</identifier><identifier type="DOI">10.1002/prot.21977</identifier><identifier type="ArticleID">PROT21977</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2008 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-L0C46X92-X">wiley</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-1GHF12RV-X/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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