Self-assembly of amyloid-forming peptides by molecular dynamics simulations.
Identifieur interne : 002953 ( Main/Exploration ); précédent : 002952; suivant : 002954Self-assembly of amyloid-forming peptides by molecular dynamics simulations.
Auteurs : Guanghong Wei [République populaire de Chine] ; Wei Song ; Philippe Derreumaux ; Normand MousseauSource :
- Frontiers in bioscience : a journal and virtual library [ 1093-9946 ] ; 2008.
Descripteurs français
- KwdFr :
- MESH :
- biosynthèse : Amyloïde.
- métabolisme : Maladies neurodégénératives, Peptides.
- physiopathologie : Maladies neurodégénératives.
- Amyloïde, Dimérisation, Humains, Modèles moléculaires, Oligopeptides, Peptides, Protéines, Solvants, Thermodynamique, bêta-2-Microglobuline.
English descriptors
- KwdEn :
- Amyloid (biosynthesis), Amyloid (chemistry), Dimerization, Humans, Models, Molecular, Neurodegenerative Diseases (metabolism), Neurodegenerative Diseases (physiopathology), Oligopeptides (chemistry), Peptides (chemistry), Peptides (metabolism), Proteins (chemistry), Solvents, Thermodynamics, beta 2-Microglobulin (chemistry).
- MESH :
- chemical , biosynthesis : Amyloid.
- chemical , chemistry : Amyloid, Oligopeptides, Peptides, Proteins, beta 2-Microglobulin.
- metabolism : Neurodegenerative Diseases, Peptides.
- physiopathology : Neurodegenerative Diseases.
- Dimerization, Humans, Models, Molecular, Solvents, Thermodynamics.
Abstract
Protein aggregation is associated with many neurodegenerative diseases. Understanding the aggregation mechanisms is a fundamental step in order to design rational drugs interfering with the toxic intermediates. This self-assembly process is however difficult to observe experimentally, which gives simulations an important role in resolving this problem. This study shows how we can proceed to gain knowledge about the first steps of aggregation. We first start by characterizing the free energy surface of the Abeta (16-22) dimer, a well-studied system numerically, using molecular dynamics simulations with OPEP coarse-grained force field. We then turn to the study of the NHVTLSQ peptide in 4-mers and 16-mers, extracting information on the onset of aggregation. In particular, the simulations indicate that the peptides are mostly random coil at room temperature, but can visit diverse amyloid-competent topologies, albeit with a low probability. The fact that the 16-mers constantly move from one structure to another is consistent with the long lag phase measured experimentally, but the rare critical steps leading to the rapid formation of amyloid fibrils still remain to be determined.
DOI: 10.2741/3109
PubMed: 18508615
Affiliations:
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Le document en format XML
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Derreumaux</name></author><author><name sortKey="Mousseau, Normand" sort="Mousseau, Normand" uniqKey="Mousseau N" first="Normand" last="Mousseau">Normand Mousseau</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2008">2008</date><idno type="RBID">pubmed:18508615</idno><idno type="pmid">18508615</idno><idno type="doi">10.2741/3109</idno><idno type="wicri:Area/PubMed/Corpus">002108</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002108</idno><idno type="wicri:Area/PubMed/Curation">002108</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002108</idno><idno type="wicri:Area/PubMed/Checkpoint">001F61</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001F61</idno><idno type="wicri:Area/Ncbi/Merge">000601</idno><idno type="wicri:Area/Ncbi/Curation">000601</idno><idno type="wicri:Area/Ncbi/Checkpoint">000601</idno><idno type="wicri:doubleKey">1093-9946:2008:Wei G:self:assembly:of</idno><idno type="wicri:Area/Main/Merge">002979</idno><idno type="wicri:Area/Main/Curation">002953</idno><idno type="wicri:Area/Main/Exploration">002953</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Self-assembly of amyloid-forming peptides by molecular dynamics simulations.</title><author><name sortKey="Wei, Guanghong" sort="Wei, Guanghong" uniqKey="Wei G" first="Guanghong" last="Wei">Guanghong Wei</name><affiliation wicri:level="1"><nlm:affiliation>National Key Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai 200433, China. ghwei@fudan.edu.cn</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>National Key Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai 200433</wicri:regionArea><wicri:noRegion>Shanghai 200433</wicri:noRegion></affiliation></author><author><name sortKey="Song, Wei" sort="Song, Wei" uniqKey="Song W" first="Wei" last="Song">Wei Song</name></author><author><name sortKey="Derreumaux, Philippe" sort="Derreumaux, Philippe" uniqKey="Derreumaux P" first="Philippe" last="Derreumaux">Philippe Derreumaux</name></author><author><name sortKey="Mousseau, Normand" sort="Mousseau, Normand" uniqKey="Mousseau N" first="Normand" last="Mousseau">Normand Mousseau</name></author></analytic><series><title level="j">Frontiers in bioscience : a journal and virtual library</title><idno type="ISSN">1093-9946</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amyloid (biosynthesis)</term><term>Amyloid (chemistry)</term><term>Dimerization</term><term>Humans</term><term>Models, Molecular</term><term>Neurodegenerative Diseases (metabolism)</term><term>Neurodegenerative Diseases (physiopathology)</term><term>Oligopeptides (chemistry)</term><term>Peptides (chemistry)</term><term>Peptides (metabolism)</term><term>Proteins (chemistry)</term><term>Solvents</term><term>Thermodynamics</term><term>beta 2-Microglobulin (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amyloïde ()</term><term>Amyloïde (biosynthèse)</term><term>Dimérisation</term><term>Humains</term><term>Maladies neurodégénératives (métabolisme)</term><term>Maladies neurodégénératives (physiopathologie)</term><term>Modèles moléculaires</term><term>Oligopeptides ()</term><term>Peptides ()</term><term>Peptides (métabolisme)</term><term>Protéines ()</term><term>Solvants</term><term>Thermodynamique</term><term>bêta-2-Microglobuline ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Amyloid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Amyloid</term><term>Oligopeptides</term><term>Peptides</term><term>Proteins</term><term>beta 2-Microglobulin</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Amyloïde</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neurodegenerative Diseases</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Maladies neurodégénératives</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Maladies neurodégénératives</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Neurodegenerative Diseases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Dimerization</term><term>Humans</term><term>Models, Molecular</term><term>Solvents</term><term>Thermodynamics</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Amyloïde</term><term>Dimérisation</term><term>Humains</term><term>Modèles moléculaires</term><term>Oligopeptides</term><term>Peptides</term><term>Protéines</term><term>Solvants</term><term>Thermodynamique</term><term>bêta-2-Microglobuline</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Protein aggregation is associated with many neurodegenerative diseases. Understanding the aggregation mechanisms is a fundamental step in order to design rational drugs interfering with the toxic intermediates. This self-assembly process is however difficult to observe experimentally, which gives simulations an important role in resolving this problem. This study shows how we can proceed to gain knowledge about the first steps of aggregation. We first start by characterizing the free energy surface of the Abeta (16-22) dimer, a well-studied system numerically, using molecular dynamics simulations with OPEP coarse-grained force field. We then turn to the study of the NHVTLSQ peptide in 4-mers and 16-mers, extracting information on the onset of aggregation. In particular, the simulations indicate that the peptides are mostly random coil at room temperature, but can visit diverse amyloid-competent topologies, albeit with a low probability. The fact that the 16-mers constantly move from one structure to another is consistent with the long lag phase measured experimentally, but the rare critical steps leading to the rapid formation of amyloid fibrils still remain to be determined.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Derreumaux, Philippe" sort="Derreumaux, Philippe" uniqKey="Derreumaux P" first="Philippe" last="Derreumaux">Philippe Derreumaux</name><name sortKey="Mousseau, Normand" sort="Mousseau, Normand" uniqKey="Mousseau N" first="Normand" last="Mousseau">Normand Mousseau</name><name sortKey="Song, Wei" sort="Song, Wei" uniqKey="Song W" first="Wei" last="Song">Wei Song</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Wei, Guanghong" sort="Wei, Guanghong" uniqKey="Wei G" first="Guanghong" last="Wei">Guanghong Wei</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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