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http://dx.doi.org/10.5012/bkcs.2009.30.8.1845

Dimerization of Fibril-forming Segments of α-Synuclein  

Yoon, Je-Seong (School of Chemistry, Seoul National University)
Jang, Soon-Min (Department of Chemistry, Sejong University)
Lee, Kyung-Hee (Department of Chemistry, Sejong University)
Shin, Seok-Min (School of Chemistry, Seoul National University)
Publication Information
Bulletin of the Korean Chemical Society / v.30, no.8, 2009 , pp. 1845-1850 More about this Journal
Abstract
We have performed replica-exchange molecular dynamics (REMD) simulations on the dimer formation of fibrilforming segments of $\alpha$-Synuclein (residues 71 - 82) using implicit solvation models with two kinds of force fields- AMBER parm99SB and parm96. We observed spontaneous formation of dimers from the extensive simulations, demonstrating the self-aggregating and fibril forming properties of the peptides. Secondary structure profile and clustering analysis showed that dimers with antiparallel $\beta$-sheet conformations, stabilized by well-defined hydrogen boding, are major species corresponding to global free energy minimum. Parallel dimers with partial $\beta$-sheets are found to be off-pathway intermediates. The relative instability of the parallel arrangements is due to the repulsive interactions between bulky and polar side chains as well as weaker backbone hydrogen bonds.
Keywords
$\alpha$-Synuclein; Replica-exchange molecular dynamics (REMD); Fibril formation; Antiparallel $\beta$-sheet;
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1 Uversky, V. N.; Li, J.; Fink, A. L. J. Biol. Chem. 2001, 276, 10737   DOI   ScienceOn
2 Uversky, V. N. J. Biomol. Struct. Dyn. 2003, 21, 211   DOI
3 Lee, I.-H.; Kim, H. J.; Lee, C.-H.; Paik, S. R. Bull. Kor. Chem. Soc. 2006, 27, 1001   DOI   ScienceOn
4 Ulmer, T. S.; Bax, A.; Cole, N. B.; Nussbaum, R. L. J. Biol. Chem. 2005, 280, 9595   DOI   ScienceOn
5 Iwai, A. I.; Yoshimoto, M.; Masliah, E.; Saitoh, T. Biochemistry 1995, 34, 10139   DOI   ScienceOn
6 Yoon, J.; Park, J.; Jang, S.; Lee, K.; Shin, S. J. Biomol. Struct. Dyn. 2008, 25, 505   DOI
7 Yoon, J.; Park, J.; Jang, S.; Lee, K.; Shin, S. Bull. Kor. Chem. Soc. 2009, 30, 623   DOI   ScienceOn
8 Giasson, B. I.; Murray, I. V. J.; Trojanowski, J. Q.; Lee, V. M.-Y. J. Biol. Chem. 2001, 276, 2380   DOI   ScienceOn
9 Pawar, A. P.; Dubay, K. F.; Zurdo, J.; Chiti, F.; Vendruscolo, M.; Dobson, C. M. J. Mol. Biol. 2005, 350, 379   DOI   ScienceOn
10 Kim, S.; Seo, J.; Suh, Y. Park. Rel. Dis. 2004, 10, S9   DOI   ScienceOn
11 Eliezer, D.; Kutluay, E.; Bussell, Jr., R.; Browne, G. J. Mol. Biol. 2001, 307, 1061   DOI   ScienceOn
12 Sugita, Y.; Okamoto, Y. Chem. Phys. Lett. 1999, 314, 141   DOI   ScienceOn
13 Skovronsky, D. M.; Lee, V. M.-Y.; Trojanowski, J. Q. Annu. Rev. Pathol. Mech. Dis. 2006, 1, 151   DOI   ScienceOn
14 Chiti, F.; Dobson, C. M. Annu. Rev. Biochem. 2006, 75, 333   DOI   ScienceOn
15 Fink, A. Acc. Chem. Res. 2006, 39, 628   DOI   ScienceOn
16 Uversky, V. N.; Oldfield, C. J.; Dunker, A. K. Annu. Rev. Biophys. 2008, 37, 215   DOI   ScienceOn
17 Dunker, A. K.; Lawson, J. D.; Brown, C. J.; Williams, R. M.; Romero, P.; Oh, J. S.; Oldfield, C. J.; Campen, A. M.; Ratliff, C. M.; Hipps, K. W.; Ausio, J.; Nissen, M. S.; Reeves, R.; Kang, C.; Kissinger, C. R.; Bailey, R. W.; Griswold, M. D.; Chiu, W.; Garner, E. C.; Obradovic, Z. J. Mol. Graph. Modell. 2001, 19, 26   DOI   ScienceOn
18 Uversky, V. Prot. Sci. 2002, 11, 739   DOI   ScienceOn
19 Ma, B.; Nussinov, R. Curr. Opin. Chem. Biol. 2006, 10, 445   DOI   ScienceOn
20 Teplow, D. B.; Lazo, N. D.; Bitan, G.; Bernstein, S.; Wyttenbach, T.; Bowers, M. T.; Baumketner, A.; Shea, J. E.; Urbanc, B.; Cruz, L.; Borreguero, J.; Stanley, H. E. Acc. Chem. Res. 2006, 39, 635   DOI   ScienceOn
21 L$\ddot{u}$cking, C. B.; Brice, A. Cell. Mol. Life. Sci. 2000, 57, 1894   DOI   ScienceOn
22 Spillantini, M. G.; Schmidt, M. L.; Lee, V. M.; Trojanowski, J. Q.; Jakes, R.; Goedert, M. Nature 2006, 388, 839   DOI   ScienceOn
23 Shults, C. W. Proc. Natl. Acad. Sci. USA 2006, 103, 1661   DOI   ScienceOn
24 Shell, M. S.; Ritterson, R.; Dill, K. A. J. Phys. Chem. B 2008, 112, 6878   DOI   ScienceOn
25 Dobson, C. M. Nature 2003, 426, 884   DOI   ScienceOn
26 Ross, C. A.; Poirier, M. A. Nat. Med. 2004, 10, S10   DOI   ScienceOn
27 Case, D. A.; Darden, T. A.; Cheatham, T. E. I.; Simmerling, C. L.; Wang, J.; Duke, R. E.; Luo, R.; Merz, K. M.; Wang, B.; Pearlman, D. A.; Crowley, M.; Brozell, S.; Tsui, V.; Gohlke, H.; Mongan, J.; Hornak, V.; Cui, G.; Beroza, P.; Schafmeister, C.; Caldwell, J. W.; Ross, W. S.; Kollman, P. A. AMBER8 University of California, San Francisco, 2004
28 Mongan, J.; Simmerling, C.; McCammon, J. A.; Case, D. A.; Onufriev, A. J. Chem. Theory Comput. 2006, 3, 156   DOI   ScienceOn
29 Onufriev, A.; Bashford, D.; Case, D. A. Proteins 2004, 55, 383   DOI   ScienceOn
30 Ryckaert, J. P.; Cicotti, G.; Berendsen, H. J. C. J. Comput. Phys. 1977, 23, 327   DOI   ScienceOn
31 Shell, M. S.; Ritterson, R.; Dill, K. A. J. Phys. Chem. B 2008, 112, 6878   DOI   ScienceOn
32 Zhang, W.; Wu, C.; Duan, Y. J. Chem. Phys. 2005, 123, 154105   DOI   ScienceOn