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. Computational optimization approaches , however, allow us to obtain a description of prion 113-120 peptide at a microscopic level. Zhang (J. Mol. Model., 2010, DOI: 10.1007/s00894-010-0691-y) using the traditional local optimization search steepest descent and conjugate gradient methods hybridized with the standard global optimization search simulated annealingmethod successfully constructed three atomic-resolution structures of prion AGAAAAGA amyloid fibrils. Zhang pointed out, basing on the NNQNTF peptide of elk prion 173--178 (3FVA.pdb released on 30-JUN-2009 in the Protein Data Bank), new models for prion AGAAAAGA amyloid fibrils might also be able to be constructed. In this paper , using the hybrid local and global optimization search methods, the author successfully constructs another two optimal atomic-resolution amyloid fibril models for the prion AGAAAAGA palindrome. According to Brown (Mol. Cell. Neurosci., 2000, Vol. 15, pp. 66--78), AGAAAAGA is an inhibitor of infectious prions. These atomic-resolution structures of the AGAAAAGA amyloid fibrils constructed might be useful in furthering the goals of medicinal chemistry for controlling prion diseases.
X-ray crystallography is a powerful tool to determine the protein 3D structure. However, it is time-consuming and expensive, and not all proteins can be successfully crystallized, particularly for membrane proteins. Although nuclear magnetic resonance (NMR) spectroscopy is indeed a very powerful tool in determining the 3D structures of membrane proteins, it is also time-consuming and costly. To the best of the authors' knowledge , there is little structural data available on the AGAAAAGA palindrome in the hydrophobic region (113-120) of prion proteins due to the noncrystalline and insoluble nature of the amyloid fibril , although many experimental studies have shown that this region has amyloid fibril forming properties and plays an important role in prion diseases. In view of this, the present study is devoted to address this problem from computational approaches such as global energy optimization, simulated annealing, and structural bioinformatics. The optimal atomic-resolution structures of prion AGAAAAGA amyloid fibils reported in this paper have a value to the scientific community in its drive to find treatments for prion diseases.
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To date
X-ray crystallography is a powerful tool to determine the protein 3D structure. However, it is time-consuming and expensive, and not all proteins can be successfully crystallized, particularly for membrane proteins. Although nuclear magnetic resonance (NMR) spectroscopy is indeed a very powerful tool in determining the 3D structures of membrane proteins, it is also time-consuming and costly. To the best of the authors' knowledge
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due to the noncrystalline and insoluble nature of the amyloid fibril
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. 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. Computational optimization approaches , however, allow us to obtain a description of prion 113-120 peptide at a microscopic level. Zhang (J. Mol. Model., 2010, DOI: 10.1007/s00894-010-0691-y) using the traditional local optimization search steepest descent and conjugate gradient methods hybridized with the standard global optimization search simulated annealingmethod successfully constructed three
and plays an important role in prion diseases. In view of this, the present study is devoted to address this problem from computational approaches such as global energy optimization, simulated annealing, and structural bioinformatics. The optimal
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fibrils. Zhang pointed out, basing on the NNQNTF peptide of elk prion 173--178 (3FVA.pdb released on 30-JUN-2009 in the Protein Data Bank), new models for prion AGAAAAGA amyloid fibrils might also be able to be constructed. In this paper , using the hybrid local and global optimization search methods, the author successfully constructs another two optimal atomic-resolution amyloid fibril models for the prion AGAAAAGA palindrome. According to Brown (Mol. Cell. Neurosci., 2000, Vol. 15, pp. 66--78), AGAAAAGA is an inhibitor of infectious prions. These atomic-resolution structures of the AGAAAAGA amyloid fibrils constructed might be useful in furthering the goals of medicinal chemistry for controlling
fibils reported in this paper have a value to the scientific community in its drive to find treatments for