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

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.

Evaluation of extracellular matrix mimetic laminin bioactive peptide and elastin‐like polypeptide

“…7,8 Since they promote diverse biologically relevant activities, including cell migration, neurite outgrowth, differentiation, and tumor angiogenesis and metastasis, they are a promising therapeutic target for tissue repair. [9][10][11] Several bioactive peptides from mouse laminin α1 chain were previously identified by screening the full-length protein using a library of synthetic peptides that span its entire amino acid sequence. Small peptides approximately 12 amino acids in length were synthesized, where each peptide consisted of an overlap with four amino acids with the preceding peptide.…”

Structural Basis of Fullerene Derivatives as Novel Potent Inhibitors of Protein Tyrosine Phosphatase 1B: Insight into the Inhibitory Mechanism through Molecular Modeling Studies

“…The data can be visualized by means of correlation maps calculation using the equation The covariance matrix map allows the identification of residue pairs with correlated and anticorrelated motion . The projections of the original structures onto the eigenvectors of the related principal components are represented as plots of the cross-correlation map. , …”

Conformation Analysis of Peptides Derived from Laminin Alpha 1–2 Chain Using Molecular Dynamics Simulation

“…Formerly, we performed conformation analysis of peptides (EF1, sEF1 and EF2) in LG4 modules using molecular dynamics simulations. Our previous results showed that EF1 has hairpin-like structure (EF2 does not have), and we indicated relation between activities and the structure [6][7]. In this paper, we investigate dynamics behavior of EF1 and EF2 peptides at 300K and 1bar (NPT ensemble).…”