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pagetitle-crest Simulating Coarse Grained Models of Self Assembling Peptide Fibres (SAFs)

T Stedall & S Hanna

Collaborators: D Woolfson, B Bromley & P King (Chemistry)

There is currently much interest in peptide self-assembly, which promises novel functional and responsive biomaterials. Self assembly has applications in tissue engineering where peptides can act as an external scaffold and influence stem cell differentiation, and is key in understanding degenerative diseases such as Alzheimers.

The SAF system comprises of two 28 residue synthetic peptides, designed de novo. It is the work of Dek Woolfson and co-workers, see the group's website for more information. The system self assembles to fibres that are typically ~ 50-100 nm in width and tens of microns in length, as seen in these electron microscopy images.



saf_sem

Image used with permission from: Smith, A. M. and Banwell, E. F. and Edwards, W. R. and Pandya, M. J. and Woolson, D. N., Engineering increased stability into self-assembled protein fibers, Advanced Functional Materials 16(8), 1022-1030 (2006).

A heptad repeat HPPHPPP, where H denotes a hydrophobic residue and P a polar one, gives rise to alpha helices with the hydrophobic residues occurring in the same position position along their length. These helices subsequently form coiled-coils such that the hydrophobic residues occur on their inside. Specific placement of key asparagine residues in the sequence ensures offset assembly of the peptide species that promote longitudinal assembly and charged residues stabilize lateral assembly.

We perform Monte Carlo simulations of coarse grained models of this peptide system. We aim to understand in detail the nucleation and growth of the SAF system, particularly with regard to nucleation theory. Hence we require a model that is detailed enough to be useful but that is computationally feasible. In the first instance we model the peptides as one dimensional rods interacting via point potentials. We observe fibre formation in both homogeneously and heterogeneously nucleated systems in NVT, NpT and μVT ensembles.

saf_sim

The figure shows a snapshot of a μVT simulation, where each peptide species is represented as a red-blue rod, where red binds to red and blue to blue. Simulations are performed on Bristol's Advanced Computing Research Centre (ACRC) BabyBlue Crystal, http://www.acrc.bris.ac.uk.

We have refined the above by modelling the SAFs as half hexagonal prisms to encapsulate the both the formation of coiled coils and assembly of these into fibres. In the future we will develop more sophisticated coarse grained models and perform detailed atomistic modelling. Through both of these approaches we hope to increase our understanding of the SAF system and more generally of peptide self assembly.