6 research outputs found
Evaluating force field accuracy with long-time simulations of a tryptophan zipper peptide
We have combined a custom implementation of the fast multiple-time-stepping
LN integrator with parallel tempering to explore folding properties of small
peptides in implicit solvent on the time scale of microseconds. We applied this
algorithm to the synthetic {\beta}-hairpin trpzip2 and one of its sequence
variants W2W9. Each simulation consisted of over 12 {\mu}s of aggregated
virtual time. Several measures of folding behavior showed convergence, allowing
comparison with experimental equilibrium properties. Our simulations suggest
that the electrostatic interaction of tryptophan sidechains is responsible for
much of the stability of the native fold. We conclude that the ff99 force field
combined with ff96 {\phi} and {\psi} dihedral energies and implicit solvent can
reproduce plausible folding behavior in both trpzip2 and W2W9.Comment: 10 pages, 11 figures, submitted to the Journal of Chemical Physics on
June 28, 201
Engineering Amyloid Fibrils from β‑Solenoid Proteins for Biomaterials Applications
Nature provides numerous examples of self-assembly that can potentially be implemented for materials applications. Considerable attention has been given to one-dimensional cross-β or amyloid structures that can serve as templates for wire growth or strengthen materials such as glue or cement. Here, we demonstrate controlled amyloid self-assembly based on modifications of β-solenoid proteins. They occur naturally in several contexts (e.g., antifreeze proteins, drug resistance proteins) but do not aggregate <i>in vivo</i> due to capping structures or distortions at their ends. Removal of these capping structures and regularization of the ends of the spruce budworm and rye grass antifreeze proteins yield micron length amyloid fibrils with predictable heights, which can be a platform for biomaterial-based self-assembly. The design process, including all-atom molecular dynamics simulations, purification, and self-assembly procedures are described. Fibril formation with the predicted characteristics is supported by evidence from thioflavin-T fluorescence, circular dichroism, dynamic light scattering, and atomic force microscopy. Additionally, we find evidence for lateral assembly of the modified spruce budworm antifreeze fibrils with sufficient incubation time. The kinetics of polymerization are consistent with those for other amyloid formation reactions and are relatively fast due to the preformed nature of the polymerization nucleus