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Molecular Dynamics Simulations Of Peptides Containing An Unnatural Amino Acid: Dimerization, Folding, And Protein Binding, Haibo Yu, Xavier Daura, Wilfred Van Gunsteren

Faculty of Science - Papers (Archive)

We have performed molecular dynamics (MD) simulations to study the dimerization, folding, and binding to a protein of peptides containing an unnatural amino acid. NMR studies have shown that the substitution of one residue in a tripeptide β-strand by the unnatural amino acid Hao (5-HO2CCONH-2-MeO-C6H3-CO-NHNH2) modifies the conformational flexibility of the β-strand and the hydrogen-bonding properties of its two edges: The number of hydrogen-bond donors and acceptors increases at one edge, whereas at the other, they are sterically hindered. In simulations in chloroform, the Hao-containing peptide 9 (i-PrCO-Phe-Hao-Val-NHBu) forms a β-sheet–like hydrogen-bonded dimer, in good agreement with the available experimental …