Hayward, S., and Milner-White, E.J. (2011) Simulation of the β- to α-sheet transition results in a twisted sheet for antiparallel and an α-nanotube for parallel strands: implications for amyloid format. Proteins: Structure Function and Bioinformatics, 79(11), pp. 3193-3207. (doi:10.1002/prot.23154)
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Publisher's URL: http://dx.doi.org/10.1002/prot.23154
alpha-sheet has been proposed to be the main constituent of the toxic amyloid intermediate. Molecular dynamics simulations on proteins known to be involved in amyloid diseases have demonstrated that beta-sheet can, under certain conditions, spontaneously convert to alpha-sheet via beta beta ->alpha(R)alpha(L) peptide-plane flipping. Using torsion-angle driving to simulate this flip the transition has been investigated for parallel and antiparallel sheets. Concerted and sequential flipping processes were simulated, the former allowing direct calculation of helical parameters. For antiparallel sheet, the strands tend to splay apart during the transition. This can be understood by consideration of the geometry of repeating dipeptide conformations. At the end of the transition antiparallel alpha-sheet is slightly twisted, comprising gently curving strands. In parallel sheet, the strands maintain identical conformations and stay hydrogen bonded during the transition as they curl up to suggest a hitherto unseen structure, the multi-helix alpha-nanotube. Intriguingly, the alpha-nanotube has some of the characteristics of the parallel beta-helix, a single-helix structure also implicated in amyloid. Unlike the beta-helix, alpha-nanotube formation could involve identical strands aligning with each other in register as in most amyloids. Proteins 2011;79:3193-3207. (C) 2011 Wiley-Liss, Inc
|Glasgow Author(s) Enlighten ID:||Milner-White, Professor E|
|Authors:||Hayward, S., and Milner-White, E.J.|
|College/School:||College of Medical Veterinary and Life Sciences|
|Journal Name:||Proteins: Structure Function and Bioinformatics|