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- Title
Time-averaged predictions of folded and misfolded peptides using a reduced physicochemical model.
- Authors
Clarke, Oliver J.; Parker, Martin J.
- Abstract
Energy-based methods for calculating time-averaged peptide structures are important for rational peptide design, for defining local structure propensities in large protein chains, and for exploring the sequence determinants of amyloid formation. High-end methods are currently too slow to be practicable, and will remain so for the foreseeable future. The challenge is to create a method that runs quickly on limited computer resources and emulates reality sufficiently well. We have developed a simplified off-lattice protein model, incorporating semi-empirical physicochemical potentials, and combined it with an efficient Monte Carlo method for calculating time-averaged peptide structures. Reasonably accurate predictions are found for a set of small α-helical and β-hairpin peptides, and we demonstrate a potential application in measuring local structure propensities in protein chains. Time-averaged structures have also been calculated for a set of small peptides known to form β-amyloid fibrils. The simulations were of three interacting peptides, and in each case the time-averaged structure describes a three-stranded β-sheet. The performance of our method in measuring the propensities of small peptides to self-associate into possible prefibrillar species compares favorably with more detailed and CPU-intensive approaches. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
- Subjects
PROTEIN folding; PROTEIN conformation; AMYLOID; PEPTIDES; MONTE Carlo method
- Publication
Journal of Computational Chemistry, 2008, Vol 29, Issue 7, p1177
- ISSN
0192-8651
- Publication type
Article
- DOI
10.1002/jcc.20879