Reconstruction and stability of secondary structure elements in the context of protein structure prediction
Podtelezhnikov, Alexei A. and Wild, David L.. (2009) Reconstruction and stability of secondary structure elements in the context of protein structure prediction. Biophysical Journal, Vol.96 (No.11). pp. 4399-4408. ISSN 0006-3495Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.bpj.2009.02.057
Efficient and accurate reconstruction of secondary structure elements in the context of protein structure prediction is the major focus of this work. We present a novel approach capable of reconstructing alpha-helices and beta-sheets in atomic detail. The method is based on Metropolis Monte Carlo simulations in a force field of empirical potentials that are designed to stabilize secondary structure elements in room-temperature simulations. Particular attention is paid to lateral side-chain interactions in beta-sheets and between the turns of alpha-helices, as well as backbone hydrogen bonding. The force constants are optimized using contrastive divergence, a novel machine learning technique, from a data set of known structures. Using this approach, we demonstrate the applicability of the framework to the problem of reconstructing the overall protein fold for a number of commonly studied small proteins, based on only predicted secondary structure and contact map. For protein G and chymotrypsin inhibitor 2, we are able to reconstruct the secondary structure elements in atomic detail and the overall protein folds with a root mean-square deviation of <10 angstrom. For cold-shock protein and the SH3 domain, we accurately reproduce the secondary structure elements and the topology of the 5-stranded beta-sheets, but not the barrel structure. The importance of high-quality secondary structure and contact map prediction is discussed.
|Item Type:||Journal Article|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Divisions:||Faculty of Science > Centre for Systems Biology|
|Journal or Publication Title:||Biophysical Journal|
|Official Date:||3 June 2009|
|Number of Pages:||10|
|Page Range:||pp. 4399-4408|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||National Institutes of Health|
|Grant number:||1 P01 GM63208|
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