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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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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. |
format | Online Article Text |
id | pubmed-4759364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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