Dr. Chin-Kun Hu, a Research Fellow at the Laboratory of Statistical and Computational Physics of the Institute of Physics at Academia Sinica, and his collaborators have recently identified a number of key factors governing protein aggregation. It is important to enhance the understanding of protein aggregation, which is thought to have played an important role in the onset and progression of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. The group’s findings have been published in a series of papers in Physical Review Letters (PRL) and Journal of the Physical Society of Japan (JPSJ). 

Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinocerebellar atrophy, and frontotemporal lobar degeneration, are caused by progressive loss of structure and function of neurons (including death of neurons) as a result of protein aggregation. For example, Alzheimer's disease is thought to be related to the aggregation of Aβ40 (a protein made up of 40 amino acids) and Aβ42 (a protein made up of 42 amino acids), while Huntington's disease and spinocerebellar atrophy are related to the aggregation of PolyQ (a protein with a long sequence of the amino acid glutamine).

In a study published in Physical Review Letters on 19 November, 2010, Dr. Chin-Kun Hu and his collaborators working in Poland, Vietnam, and the US, used a lattice model to study the aggregation rates of proteins. They found that the probability of a protein sequence appearing in an aggregated conformation can be used to determine the temperature at which the protein can aggregate most easily. They also found that the time taken for the protein to aggregate correlated to the strength of interactions between charged amino acids, which is consistent with previous experimental observations.

In other four articles published in the Journal of the Physical Society of Japan in February, May and October 2010, Dr. Hu, together with Dr. Wen-Jong Ma (now a member of the faculty at the Graduate Institute of Applied Physics, National Chengchi University, Taiwan), employed molecular dynamics to study the relaxation and aggregation of protein chains under various conditions. They found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, the protein chains tend to aggregate at lower temperatures. This finding has contributed to the understanding of the aggregation of Aβ40 and Aβ42 in Alzheimer's disease.

As the next step of the project, Dr. Hu said that he and his collaborators would like to combine the results from computer simulations and analytic calculations with experimental data in an attempt to formulate a general theory of protein aggregation to enable prediction of the influence of environment, mutation and drugs on protein aggregation rates, and also to predict the conditions most likely to prohibit protein aggregation.

The article entitled “Factors Governing Fibrillogenesis of Polypeptide Chains Revealed by Lattice Models” published in Physical Review Letters is available at the journal’s website at: http://prl.aps.org/abstract/PRL/v105/i21/e218101. The full list of authors is: Mai Suan Li, Nguyen Truong Co, Govardhan Reddy, Chin-Kun Hu, J. E. Straub, and D. Thirumalai. The other four articles are available at the website of the Journal of the Physical Society of Japan (JPSJ) at: http://jpsj.ipap.jp/

Related websites:
Laboratory of Statistical and Computational Physics: https://www.sinica.edu.tw/CP/562#/~statphys