Folding of an alpha-helical peptide constrained by the presence of a chemical crosslink

The folding process of EAAAR (sequence Acetyl-EACAREAAAREAACRQ-NH2), a 16-residue cross-linked α-helical peptide, is sampled by implicit solvent (SASA) molecular dynamics simulations. The cross-linker incorporates a photoisomerizable azobenzene moiety and can adopt two conformations: the cis (closed) conformation and the trans (opened) conformation. Only the latter favors the formation of an α-helix. Switching the liker from cis to trans allows the study of the folding process of EAAAR. At 281K, 50 Langevin dynamics runs of 4 μs each were started from the equilibrium cis conformation of the EAAAR peptide previously sampled by replica exchange molecular dynamics. One of these 4μs-long dynamic runs is shown. At the beginning, the linker is in its cis conformation. Upon ultrafast cross-linker isomerization (cis to trans transition) the folding of an alpha-helix (green ribbon) occurs.