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Computational De Novo Design of a Self-Assembling Peptide with Predefined Structure.

Kaltofen, Sabine LU ; Li, Chenge; Huang, Po-Ssu; Serpell, Louise C; Barth, Andreas and André, Ingemar LU (2015) In Journal of Molecular Biology 427(2). p.550-562
Abstract
Protein and peptide self-assembly is a powerful design principle for engineering of new biomolecules. More sophisticated biomaterials could be built if both the structure of the overall assembly and that of the self-assembling building block could be controlled. To approach this problem, we developed a computational design protocol to enable de novo design of self-assembling peptides with predefined structure. The protocol was used to design a peptide building block with a βαβ fold that self-assembles into fibrillar structures. The peptide associates into a double β-sheet structure with tightly packed α-helices decorating the exterior of the fibrils. Using circular dichroism, Fourier transform infrared spectroscopy, electron microscopy and... (More)
Protein and peptide self-assembly is a powerful design principle for engineering of new biomolecules. More sophisticated biomaterials could be built if both the structure of the overall assembly and that of the self-assembling building block could be controlled. To approach this problem, we developed a computational design protocol to enable de novo design of self-assembling peptides with predefined structure. The protocol was used to design a peptide building block with a βαβ fold that self-assembles into fibrillar structures. The peptide associates into a double β-sheet structure with tightly packed α-helices decorating the exterior of the fibrils. Using circular dichroism, Fourier transform infrared spectroscopy, electron microscopy and X-ray fiber diffraction, we demonstrate that the peptide adopts the designed conformation. The results demonstrate that computational protein design can be used to engineer protein and peptide assemblies with predefined three-dimensional structures, which can serve as scaffolds for the development of functional biomaterials. Rationally designed proteins and peptides could also be used to investigate the subtle energetic and entropic tradeoffs in natural self-assembly processes and the relation between assembly structure and assembly mechanism. We demonstrate that the de novo designed peptide self-assembles with a mechanism that is more complicated than expected, in a process where small changes in solution conditions can lead to significant differences in assembly properties and conformation. These results highlight that formation of structured protein/peptide assemblies is often dependent on the formation of weak but highly precise intermolecular interactions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Molecular Biology
volume
427
issue
2
pages
550 - 562
publisher
Elsevier
external identifiers
  • pmid:25498388
  • wos:000348888200029
  • scopus:84920860615
ISSN
1089-8638
DOI
10.1016/j.jmb.2014.12.002
language
English
LU publication?
yes
id
a6255f98-2205-465b-97ee-0b211def62c2 (old id 4908514)
date added to LUP
2015-01-13 17:02:03
date last changed
2017-07-09 03:10:53
@article{a6255f98-2205-465b-97ee-0b211def62c2,
  abstract     = {Protein and peptide self-assembly is a powerful design principle for engineering of new biomolecules. More sophisticated biomaterials could be built if both the structure of the overall assembly and that of the self-assembling building block could be controlled. To approach this problem, we developed a computational design protocol to enable de novo design of self-assembling peptides with predefined structure. The protocol was used to design a peptide building block with a βαβ fold that self-assembles into fibrillar structures. The peptide associates into a double β-sheet structure with tightly packed α-helices decorating the exterior of the fibrils. Using circular dichroism, Fourier transform infrared spectroscopy, electron microscopy and X-ray fiber diffraction, we demonstrate that the peptide adopts the designed conformation. The results demonstrate that computational protein design can be used to engineer protein and peptide assemblies with predefined three-dimensional structures, which can serve as scaffolds for the development of functional biomaterials. Rationally designed proteins and peptides could also be used to investigate the subtle energetic and entropic tradeoffs in natural self-assembly processes and the relation between assembly structure and assembly mechanism. We demonstrate that the de novo designed peptide self-assembles with a mechanism that is more complicated than expected, in a process where small changes in solution conditions can lead to significant differences in assembly properties and conformation. These results highlight that formation of structured protein/peptide assemblies is often dependent on the formation of weak but highly precise intermolecular interactions.},
  author       = {Kaltofen, Sabine and Li, Chenge and Huang, Po-Ssu and Serpell, Louise C and Barth, Andreas and André, Ingemar},
  issn         = {1089-8638},
  language     = {eng},
  number       = {2},
  pages        = {550--562},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Biology},
  title        = {Computational De Novo Design of a Self-Assembling Peptide with Predefined Structure.},
  url          = {http://dx.doi.org/10.1016/j.jmb.2014.12.002},
  volume       = {427},
  year         = {2015},
}