Simulations map how sequence shapes folding and assembly of glycine-repeat peptides on graphite

Summary. Researchers at the Universidad de Talca in Chile, Stanford University and Kansas State University reported in the Journal of Chemical Information and Modeling, published online on 9 October, molecular simulations of cyclic peptides made of glycine-X repeats at the interface between graphite and water. Earlier simulations and experiments had shown that such peptides fold into beta-hairpins on graphite and then self-assemble through hydrogen bonds between neighbouring molecules. The new study asks how the hairpin turn sequence, the strand length and the identity of the X amino acid affect both steps. Simulations of relatively large systems, each starting with nine unfolded peptides, let the team observe folding and assembly happen spontaneously and compare thermodynamics, kinetics and misfolded states across sequences.

Research context (RUO). A GPGG turn enforced the desired hairpin better than GGGG or GDGG turns. The group's previous design was cyclised head to tail; here the authors show that disulfide cyclisation is a viable alternative. Strands with GT, GA, GG, GS or GD repeats, as well as charge-complementary GE/GZ pairs (Z being diaminobutyric acid), all folded correctly but differed in folding free energy, tendency to misfold, folding cooperativity and preferred alignment between molecules. GT repeats most favoured folding into the desired strands but gave the weakest assembly, while GG repeats gave the strongest assembly but misfolded more often. GA repeats showed strong cooperativity, with folding becoming more favourable when other folded peptides were present. A peptide with GE repeats on one strand and GZ on the other formed assemblies with alternating negative and positive strands. The study is computational and reports no laboratory or biological testing.