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Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation

Peptides with cell attachment activity are beneficial component of biomaterials for tissue engineering. Conformational structure is one of the important factors for the biological activities. The EF1 peptide (DYATLQLQEGRLHFMFDLG) derived from laminin promotes cell spreading and cell attachment activ...

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Autores principales: Yamada, Hironao, Mori, Sakiko, Miyakawa, Takeshi, Morikawa, Ryota, Katagiri, Fumihiko, Hozumi, Kentaro, Kikkawa, Yamato, Nomizu, Motoyoshi, Takasu, Masako
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759364/
https://www.ncbi.nlm.nih.gov/pubmed/26889829
http://dx.doi.org/10.1371/journal.pone.0149474
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author Yamada, Hironao
Mori, Sakiko
Miyakawa, Takeshi
Morikawa, Ryota
Katagiri, Fumihiko
Hozumi, Kentaro
Kikkawa, Yamato
Nomizu, Motoyoshi
Takasu, Masako
author_facet Yamada, Hironao
Mori, Sakiko
Miyakawa, Takeshi
Morikawa, Ryota
Katagiri, Fumihiko
Hozumi, Kentaro
Kikkawa, Yamato
Nomizu, Motoyoshi
Takasu, Masako
author_sort Yamada, Hironao
collection PubMed
description Peptides with cell attachment activity are beneficial component of biomaterials for tissue engineering. Conformational structure is one of the important factors for the biological activities. The EF1 peptide (DYATLQLQEGRLHFMFDLG) derived from laminin promotes cell spreading and cell attachment activity mediated by α2β1 integrin. Although the sequence of the EF2 peptide (DFATVQLRNGFPYFSYDLG) is homologous sequence to that of EF1, EF2 does not promote cell attachment activity. To determine whether there are structural differences between EF1 and EF2, we performed replica exchange molecular dynamics (REMD) simulations and conventional molecular dynamics (MD) simulations. We found that EF1 and EF2 had β-sheet structure as a secondary structure around the global minimum. However, EF2 had variety of structures around the global minimum compared with EF1 and has easily escaped from the bottom of free energy. The structural fluctuation of the EF1 is smaller than that of the EF2. The structural variation of EF2 is related to these differences in the structural fluctuation and the number of the hydrogen bonds (H-bonds). From the analysis of H-bonds in the β-sheet, the number of H-bonds in EF1 is larger than that in EF2 in the time scale of the conventional MD simulation, suggesting that the formation of H-bonds is related to the differences in the structural fluctuation between EF1 and EF2. From the analysis of other non-covalent interactions in the amino acid sequences of EF1 and EF2, EF1 has three pairs of residues with hydrophobic interaction, and EF2 has two pairs. These results indicate that several non-covalent interactions are important for structural stabilization. Consequently, the structure of EF1 is stabilized by H-bonds and pairs of hydrophobic amino acids in the terminals. Hence, we propose that non-covalent interactions around N-terminal and C-terminal of the peptides are crucial for maintaining the β-sheet structure of the peptides.
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spelling pubmed-47593642016-02-26 Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation Yamada, Hironao Mori, Sakiko Miyakawa, Takeshi Morikawa, Ryota Katagiri, Fumihiko Hozumi, Kentaro Kikkawa, Yamato Nomizu, Motoyoshi Takasu, Masako PLoS One Research Article Peptides with cell attachment activity are beneficial component of biomaterials for tissue engineering. Conformational structure is one of the important factors for the biological activities. The EF1 peptide (DYATLQLQEGRLHFMFDLG) derived from laminin promotes cell spreading and cell attachment activity mediated by α2β1 integrin. Although the sequence of the EF2 peptide (DFATVQLRNGFPYFSYDLG) is homologous sequence to that of EF1, EF2 does not promote cell attachment activity. To determine whether there are structural differences between EF1 and EF2, we performed replica exchange molecular dynamics (REMD) simulations and conventional molecular dynamics (MD) simulations. We found that EF1 and EF2 had β-sheet structure as a secondary structure around the global minimum. However, EF2 had variety of structures around the global minimum compared with EF1 and has easily escaped from the bottom of free energy. The structural fluctuation of the EF1 is smaller than that of the EF2. The structural variation of EF2 is related to these differences in the structural fluctuation and the number of the hydrogen bonds (H-bonds). From the analysis of H-bonds in the β-sheet, the number of H-bonds in EF1 is larger than that in EF2 in the time scale of the conventional MD simulation, suggesting that the formation of H-bonds is related to the differences in the structural fluctuation between EF1 and EF2. From the analysis of other non-covalent interactions in the amino acid sequences of EF1 and EF2, EF1 has three pairs of residues with hydrophobic interaction, and EF2 has two pairs. These results indicate that several non-covalent interactions are important for structural stabilization. Consequently, the structure of EF1 is stabilized by H-bonds and pairs of hydrophobic amino acids in the terminals. Hence, we propose that non-covalent interactions around N-terminal and C-terminal of the peptides are crucial for maintaining the β-sheet structure of the peptides. Public Library of Science 2016-02-18 /pmc/articles/PMC4759364/ /pubmed/26889829 http://dx.doi.org/10.1371/journal.pone.0149474 Text en © 2016 Yamada et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yamada, Hironao
Mori, Sakiko
Miyakawa, Takeshi
Morikawa, Ryota
Katagiri, Fumihiko
Hozumi, Kentaro
Kikkawa, Yamato
Nomizu, Motoyoshi
Takasu, Masako
Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation
title Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation
title_full Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation
title_fullStr Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation
title_full_unstemmed Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation
title_short Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation
title_sort structural study of cell attachment peptide derived from laminin by molecular dynamics simulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759364/
https://www.ncbi.nlm.nih.gov/pubmed/26889829
http://dx.doi.org/10.1371/journal.pone.0149474
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