Self-assembly of peptides into a β-barrel motif

We report the results of a study of the self-assembly of four minimalist peptide strands with a native beta-barrel structure. Using a soft-well potential to mimic cellular crowding, molecular dynamics simulations were performed in confining spheres of varying radii. By utilizing a previously introduced scaling factor lambda for the non-native hydrophobic interactions (0<lambda<1), we were able to study models with varying degrees of frustration. Both the thermodynamics and kinetics of a G (o) over bar -like model (lambda=0) and a highly frustrated model (lambda=0.9) were studied. Additionally, we used an extrapolation technique to investigate the thermodynamics of assembly at intermediate values of lambda. As in our earlier work [J. Chem. Phys. 118, 8106 (2003)] on a connected G (o) over bar -like model beta-barrel protein, we find that the stability of the assembled protein increases with decreasing sphere size, and that larger confining spheres result in increased assembly times. Additionally, the lambda=0 model seems to undergo distinct phase transitions during the assembly process. In contrast, the more frustrated model (lambda=0.9) appears to undergo a glasslike transition at temperatures comparable to the assembly temperature of the G (o) over bar model, and that this transition is relatively nonspecific. Our results suggest the assembly process is dependent on both sequence and environment, with implications for the formation of misassembled aggregates. (C) 2004 American Institute of Physics.