Abstract
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.
Highlights
Peptides are functional molecules that can have various biological activities, and some peptides, which are part of an original protein, can mimic the functions of the original protein
We investigated the dynamical behavior of EF1 and EF2 peptides by performing conventional molecular dynamics (MD) simulation
For the free energy landscape of each replica used for analysis, the valley for EF2 was widespread on the free energy landscape compared with the valley for EF1
Summary
Peptides are functional molecules that can have various biological activities, and some peptides, which are part of an original protein, can mimic the functions of the original protein. Laminin is a giant glycoprotein (molecular weight of around 500–900 kDa) that consists of three subunits (α, β, and γ chains) It has diverse biological activities such as the promotion of cell attachment, cell migration, tumor metastasis, neurite outgrowth and angiogenesis [4,5,6,7,8]. 19 isoforms (laminin-1 to 19) have been isolated, and these isoforms are found in diverse tissues [8,9,10,11,12,13,14,15,16] Among these isoforms, laminin-1, which consists of three subunits (α1 chain, β1 chain and γ1 chain), was discovered first [5], and it enhances diverse biological activities, such as cell attachment and cell migration [17, 18]. Nomizu et al identified several bioactive peptides that reproduce the function of part of the laminin-1 [20,21,22,23]
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