title: Optimal molecular structures of prion AGAAAAGA amyloid fibrils formatted by simulated annealing.
abstract: 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.
authors.affiliation: Victorian Life Sciences Computation Initiative, The University of Melbourne, 1-3 Hull Road, Croydon, Victoria, VIC 3136, Australia. jiapu_zhang@hotmail.com
authors.forename: Jiapu
authors.initials: J
authors.lastname: Zhang
mesh_terms: 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
chemical_list: D000682:Amyloid; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins
references.citation: J Biomol Struct Dyn. 2009 Oct;27(2):159-62
references.pmid: 19583441
references.citation: J Phys Chem B. 2006 Jan 26;110(3):1423-8
references.pmid: 16471693
references.citation: Science. 1983 May 13;220(4598):671-80
references.pmid: 17813860
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363-83
references.pmid: 9811807
references.citation: Biochem Biophys Res Commun. 2009 Feb 6;379(2):298-303
references.pmid: 19103159
references.citation: Biopolymers. 2009 Dec;91(12):1161-71
references.pmid: 19280623
references.citation: Biochemistry. 2001 Jul 10;40(27):8073-84
references.pmid: 11434776
references.citation: J Neurochem. 1999 Oct;73(4):1557-65
references.pmid: 10501201
references.citation: J Biol Chem. 2005 Jul 22;280(29):27236-43
references.pmid: 15917252
references.citation: Neuroreport. 1994 Oct 27;5(16):2057-60
references.pmid: 7865744
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14790-5
references.pmid: 14657385
references.citation: Nat Struct Mol Biol. 2009 Sep;16(9):973-8
references.pmid: 19684598
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):646-50
references.pmid: 15647363
references.citation: Nature. 1967 Sep 2;215(5105):1043-4
references.pmid: 4964084
references.citation: J Mol Graph. 1996 Feb;14(1):33-8, 27-8
references.pmid: 8744570
references.citation: Microsc Res Tech. 2001 Jul 15;54(2):71-80
references.pmid: 11455614
references.citation: Comput Biol Chem. 2009 Feb;33(1):41-5
references.pmid: 18755632
references.citation: Nature. 2007 May 24;447(7143):453-7
references.pmid: 17468747
references.citation: J Gen Virol. 2002 May;83(Pt 5):1237-1245
references.pmid: 11961279
references.citation: Bioinformatics. 2007 Sep 1;23(17):2218-25
references.pmid: 17599928
references.citation: Biophys J. 2008 Aug;95(4):1877-89
references.pmid: 18469080
references.citation: Biochemistry. 2008 Dec 16;47(50):13242-51
references.pmid: 19053276
references.citation: Biochem Biophys Res Commun. 2008 Feb 15;366(3):800-6
references.pmid: 18082625
references.citation: Biophys J. 2007 Sep 1;93(5):1484-92
references.pmid: 17483185
references.citation: J Mol Model. 2008 Oct;14(10):987-94
references.pmid: 18629550
references.citation: FASEB J. 2007 Oct;21(12):3279-87
references.pmid: 17522379
references.citation: Mol Cell Neurosci. 2000 Jan;15(1):66-78
references.pmid: 10662506
references.citation: J Mol Biol. 2008 May 16;378(5):1142-54
references.pmid: 18423487
references.citation: Science. 1982 Apr 9;216(4542):136-44
references.pmid: 6801762
references.citation: J Virol. 1998 Feb;72(2):1153-9
references.pmid: 9445012