Replica-exchange molecular dynamics simulation for understanding the initial process of amyloid peptide aggregation

Abstract

We applied replica-exchange molecular dynamics simulation to five fragments of amyloid-β peptide in order to study the mechanism of amyloid fibril formation. In this study, we calculated the free energy by focusing on how to form the β-structures to obtain the dominant structures. We classify the obtained β-structures and elucidate the order of β-structure assembly.

Keywords::

• Alzheimer's disease
• amyloid fibrils
• self-assembly
• molecular dynamics simulation
• replica-exchange method
• free energy landscape

Acknowledgements

Some of the computations were performed on the supercomputers at the Institute for Molecular Science and Center for Computational Sciences, University of Tsukuba.

Additional information

Funding

This work was supported, in part, by the French National Center for Scientific Research (CNRS) and the Institut Universitaire de France and JSPS Grants-in-Aid for Scientific Research (A) [grant number 25247071], for Scientific Research on Innovative Areas (‘Dynamical Ordering and Integrated Functions’), for the Computational Materials Science Initiative, and for High Performance Computing Infrastructure from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.