Self-assembly of peptides into a beta-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 Go-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 Go-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 Go 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.
Friedel
Miriam
M
Department of Physics, University of California, Santa Barbara, California 93106, USA.
Shea
Joan-Emma
JE
D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation
D010455:Peptides