Proteins are the biopolymers that are configured by the 20 kinds of amino acids, and they must be folded to each specific structure in order to perform their functions. However, they sometimes fold into incorrect structures, and this event is called "misfolding". There are some diseases caused by misfolding, and these disease are named "folding diseases".
Alzheimer's disease, which is our research target, is also a kind of folding disease. It is well-known that Alzheimer's disease is caused by misfolding of the amyloid-beta peptides. According to some hypothesis, the cause of Alzheimer's disease is misfolding into the beta-sheet structure of amyloid-beta peptides, and to form the insoluble fibrous proteins called "amyloid fibrils"2 .
Recently, an interesting report about the mechanisms of amyloid fibril formations has published by the experimental group. They suggested that the concentration is important for the self-assembly of amyloid fibrils1 . In order to examine concentration dependence of amyloid peptide aggregation theoretically, we have performed molecular dynamics simulations.
We prepared the systems consisted by 8 fragments of amyloid-beta(25-35). For the evaluation of volumes and concentration, we provided the constraints under conditions of implicit solvent model. And by changing the ranges of constraints, we estimated the concentration dependence of the proteins. In addition, we have applied a simulation technique called replica-exchange molecular dynamics to the systems3 . By using this method, we can explore the conformational spaces efficiently.