Optimal molecular structures of prion AGAAAAGA amyloid fibrils formatted by simulated annealing.
To date, there is little structural data available on the AGAAAAGA palindrome in the hydrophobic region (113-120) of prion proteins, although many experimental studies have shown that this region has amyloid fibril forming properties. This region belongs to the N-terminal unstructured region (1-123) of prions, the structure of which has proved hard to determine using NMR or X-ray crystallography. This paper reports the successful construction of three amyloid fibril models for this region. The models were formatted by standard simulated annealing using suitable templates from the Protein Data Bank, and were refined using several traditional optimization methods within AMBER. Because the NMR or X-ray structure of the hydrophobic region AGAAAAGA of prion proteins has not yet been determined, these models can be used as a reference for experimental studies on this region. The results presented here confirm standard simulated annealing as an effective tool in molecular modeling. The three constructed models for amyloid fibrils may be useful in furthering the goals of medicinal chemistry in this field.
Zhang
Jiapu
J
Victorian Life Sciences Computation Initiative, The University of Melbourne, 1-3 Hull Road, Croydon, Victoria, VIC 3136, Australia. jiapu_zhang@hotmail.com
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D019295:Computational Biology; D055029:Inverted Repeat Sequences; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry
D000682:Amyloid; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins
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