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Optimal molecular structures of prion AGAAAAGA amyloid fibrils formatted by simulated annealing

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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.

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Acknowledgments

The author thanks Dr. Zhuqing Zhang (Peking University, China) for his help in preparing Fig. 4. The author appreciates the Editor-in-Chief for his suggestions and the anonymous referees for their numerous insightful comments, which have greatly improved this paper. Last, but not least, thanks go to Dr. Judy-Anne Osborn of the Australian National University and staff of Springer (http://www.springer.com/) for their help in improving my English of this paper. This paper is dedicated to the memory of my PhD supervisor Professor Alex M. Rubinov; the hybrid global and local optimization search strategy [38] of this paper was learned from him and Professor Adil M. Bagirov, another PhD supervisor of mine.

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  1. Victorian Life Sciences Computation Initiative, The University of Melbourne, 1–3 Hull Road, Croydon, Victoria, VIC 3136, Australia

    Jiapu Zhang

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Zhang, J. Optimal molecular structures of prion AGAAAAGA amyloid fibrils formatted by simulated annealing. J Mol Model 17, 173–179 (2011). https://doi.org/10.1007/s00894-010-0691-y

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  • DOI: https://doi.org/10.1007/s00894-010-0691-y

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